BCCIP (BRCA2 and CDKN1A-Interacting Protein): Functional Overview OpenAI o3-deep-research-2025-06-26 113 citations 2025-12-27T15:52:44.873189

BCCIP (BRCA2 and CDKN1A-Interacting Protein): Functional Overview

Gene Identity and Conservation

BCCIP (BRCA2 and CDKN1A interacting protein, UniProt Q9P287) is a human gene coding for an evolutionarily conserved protein also known as TOK1 (www.medchemexpress.eu). This protein was originally identified by its ability to bind two key tumor suppressors: BRCA2 and the CDK inhibitor p21 (CDKN1A) (www.medchemexpress.eu) (www.nature.com). The BCCIP gene is located on chromosome 10q26.2 in humans (pmc.ncbi.nlm.nih.gov) and belongs to the BCP1 family of proteins (www.ncbi.nlm.nih.gov). Orthologs exist from yeast to mammals, reflecting a high degree of evolutionary conservation (pubmed.ncbi.nlm.nih.gov). In fact, the yeast homolog (BCP1) is essential for cell viability, and BCCIP is likewise required for survival in higher eukaryotes (www.nature.com). No other closely related proteins are present in mammals, indicating BCCIP is a unique factor without redundant paralogs (pmc.ncbi.nlm.nih.gov).

Protein Structure and Isoforms

Human BCCIP is a nuclear protein with multiple domains, including an N-terminal region that shares moderate homology with calmodulin and m-calpain (www.medchemexpress.eu). This suggests BCCIP might bind calcium ions, though direct Ca²⁺-binding activity remains to be confirmed (www.medchemexpress.eu). The protein has two major splice isoforms, BCCIPα (322 amino acids) and BCCIPβ (314 amino acids) (www.nature.com). These isoforms share an identical N-terminal ~258 amino acid region (the conserved core domain) but have distinct C-termini due to alternative splicing (www.nature.com). The divergent C-terminal tails confer different interaction capabilities. Notably, BCCIPβ contains a unique C-terminus that enables it to form a complex with ribosomal protein RPL23 (uL14) and the 60S ribosome assembly factor eIF6, a property not shared by BCCIPα (pubmed.ncbi.nlm.nih.gov). This indicates specialized functions for each isoform: for example, BCCIPβ’s tail acts as a chaperone domain for ribosomal components (pubmed.ncbi.nlm.nih.gov), whereas BCCIPα has been observed to localize strongly to centrosomes and spindle poles, suggesting a more prominent role in mitotic spindle regulation (www.nature.com). Apart from the α and β isoforms, at least one additional minor isoform (sometimes termed isoform C) has been reported, though the α and β forms are the best characterized (www.medchemexpress.eu). Importantly, the BCCIP protein has no obvious enzymatic domains and does not exhibit significant sequence similarity to proteins of known structure (pubmed.ncbi.nlm.nih.gov). This suggests it functions as an adapter or scaffold protein, mediating protein–protein interactions through its conserved domains.

Expression and Cellular Localization

BCCIP is ubiquitously expressed in human tissues, with particularly high mRNA levels in proliferative organs such as the testis and ovary (www.medchemexpress.eu). At the subcellular level, BCCIP predominantly localizes to the cell nucleus, consistent with its involvement in DNA damage response and repair processes (www.medchemexpress.eu). Immunofluorescence studies have shown that BCCIP concentrates in nuclear foci alongside BRCA2 and RAD51 upon DNA damage, reflecting its role at sites of DNA repair (pmc.ncbi.nlm.nih.gov). Intriguingly, BCCIP is also found in other cellular compartments. During interphase, a fraction of BCCIP protein localizes to the nucleolus, and this is especially true for the BCCIPβ isoform (academic.oup.com). In the nucleoli, BCCIPβ associates with ribosomal precursor complexes (as detailed below), indicating a role in ribosome biogenesis (academic.oup.com). Additionally, BCCIP has a dynamic localization during the cell cycle: as cells prepare to divide, BCCIP (notably BCCIPα) relocalizes to the centrosomes and mitotic spindle poles (www.nature.com). High-resolution microscopy confirmed BCCIP’s enrichment at the mother centriole of the centrosome in interphase and around the spindle poles in mitotic cells (www.nature.com) (www.nature.com). This centrosomal pool of BCCIP lies proximal to the subdistal appendages of the mother centriole and expands into the spindle pole matrix during mitosis (www.nature.com). Thus, BCCIP’s localization is context-dependent: it shuttles between the nucleus (DNA repair foci), nucleolus (ribosomal assembly sites), and centrosome/spindle apparatus, positioning it at multiple hubs of genome maintenance.

Role in DNA Repair and Replication Stress

One of the primary functions of BCCIP is in the DNA damage response, particularly the homologous recombination (HR) repair pathway for double-strand break repair. BCCIP was shown to bind directly to a highly conserved domain of the BRCA2 tumor suppressor (pubmed.ncbi.nlm.nih.gov) – the same region of BRCA2 that mediates RAD51 recombinase loading onto DNA. BCCIP also binds the C-terminal domain of p21^Waf1/Cip1 (CDKN1A) (pubmed.ncbi.nlm.nih.gov), linking it to cell cycle regulation (discussed later). Through its interaction with BRCA2, BCCIP associates with RAD51 and co-localizes with BRCA2/RAD51 in nuclear repair foci (pmc.ncbi.nlm.nih.gov). Functional studies provide strong evidence that BCCIP is a critical component of HR repair. In a 2005 study, knocking down BCCIP in human cells markedly disrupted HR: cells with BCCIP deficiency failed to form normal RAD51 or BRCA2 foci at DNA break sites, and their ability to carry out homologous recombination repair of double-strand breaks dropped dramatically (on the order of a 20- to 100-fold reduction in HR efficiency) (pmc.ncbi.nlm.nih.gov). Conversely, partial reduction of BRCA2 also diminished BCCIP focus formation, underscoring the interdependent relationship of BCCIP with the BRCA2/RAD51 repair machinery (pmc.ncbi.nlm.nih.gov). These results demonstrate that BCCIP is indispensable for effective HR-mediated DNA repair, likely acting as a co-factor that stabilizes or assists the BRCA2–RAD51 complex during the search for homology and strand invasion steps (pmc.ncbi.nlm.nih.gov). Consistently, cells lacking BCCIP show increased spontaneous DNA damage foci and chromosomal aberrations, indicating genomic instability even in the absence of exogenous DNA damage (journals.plos.org).

In addition to its role in double-strand break repair, BCCIP plays a key part in mitigating replication stress. Replication stress (caused by stalled or collapsed replication forks) is a major source of DNA breaks and genome instability in proliferating cells (pubmed.ncbi.nlm.nih.gov). BRCA2 and RAD51 have a well-recognized “fork-protection” function independent of their role in HR repair – they protect stalled replication forks from degradation by nucleases like MRE11 (pubmed.ncbi.nlm.nih.gov). Recent research (2022) has revealed that BCCIP is also required for this replication fork protection mechanism. Upon replication stress (for example, treatment with DNA synthesis inhibitors), BCCIP is recruited to stalled replication forks in concert with BRCA2 and RAD51 (pubmed.ncbi.nlm.nih.gov). BCCIP-deficient cells experience excessive replication fork stalling and collapse, leading to an accumulation of DNA double-strand breaks under replication stress conditions (pubmed.ncbi.nlm.nih.gov). Mechanistically, BCCIP was shown to prevent degradation of nascent DNA by MRE11 nuclease at stalled forks (pubmed.ncbi.nlm.nih.gov). In BCCIP knockdown cells, newly synthesized DNA at stalled forks is rapidly chewed back by nucleases, whereas in normal cells BCCIP (together with BRCA2/RAD51) shields the nascent DNA and stabilizes the fork structure (pubmed.ncbi.nlm.nih.gov). By preserving the integrity of stalled forks, BCCIP helps maintain genome stability during S phase and prevents the conversion of transient replication problems into permanent DNA breaks. In summary, BCCIP serves as a multifaceted guardian of genome integrity in the nucleus: it facilitates high-fidelity DNA repair via homologous recombination and protects replication forks from catastrophic collapse, thereby averting chromosomal instability that could lead to cell death or oncogenic transformation.

Role in Cell Cycle Regulation (p21 and p53 Pathway)

Beyond its direct DNA repair functions, BCCIP has a significant impact on cell cycle checkpoints, particularly the G₁/S checkpoint enforced by the p53–p21 pathway. BCCIP’s very name highlights its interaction with p21^Cip1/Waf1 (CDKN1A), a cyclin-dependent kinase inhibitor that mediates p53-dependent cell cycle arrest. BCCIP binds to the C-terminus of p21 (pubmed.ncbi.nlm.nih.gov) and has been shown to enhance p21’s ability to inhibit CDK2, thereby promoting cell cycle arrest when appropriate (www.ncbi.nlm.nih.gov). Functional studies support BCCIP as a positive regulator of the p53/p21 axis. Overexpression of BCCIP in cultured cells leads to an increase in p21 mRNA and protein levels and a consequent slowing of G₁-to-S phase progression (pubmed.ncbi.nlm.nih.gov). Conversely, depletion of BCCIP by RNA interference results in lower steady-state p21 levels and a failure to properly arrest in G₁ following DNA damage (pubmed.ncbi.nlm.nih.gov). Notably, cells with BCCIP knockdown showed an impaired G₁/S checkpoint activation after ionizing radiation, indicating that p21 could not accumulate sufficiently to halt the cell cycle (pubmed.ncbi.nlm.nih.gov). This checkpoint defect was dependent on p53: BCCIP-depleted cells had reduced p21 because BCCIP is needed for full p53 transcriptional activity on the CDKN1A gene (pubmed.ncbi.nlm.nih.gov). In other words, BCCIP regulates p53’s ability to induce p21. Researchers found that BCCIP deficiency diminishes p53 target gene activation, whereas presence of BCCIP helps maintain p53’s transactivation function (pubmed.ncbi.nlm.nih.gov). Thus, BCCIP serves as a co-factor for p53 in the DNA damage response, ensuring that p21 is upregulated to impose cell cycle arrest and allow time for DNA repair. This aligns with earlier observations that BCCIP can act as a CDK2 kinase regulator via p21 (www.medchemexpress.eu). By supporting p53 and p21, BCCIP links the DNA repair machinery to cell cycle control: if BCCIP is absent, cells not only have defective DNA repair, but also may fail to stop the cell cycle in the face of DNA damage, compounding the risk of genomic instability. Interestingly, the N-terminal half of BCCIP shares homology with calmodulin, a calcium-binding regulatory protein (www.medchemexpress.eu). This raises the possibility that BCCIP’s regulatory functions (such as modulating CDK2 or p53 activity) might be influenced by calcium or other signals, though this remains speculative.

Role in Centrosome Function and Mitosis

An unexpected but crucial function of BCCIP was discovered in the context of mitotic spindle assembly and chromosome segregation. Although BCCIP is best known for its nuclear roles, cell biology studies in the last decade revealed that BCCIP (especially the α isoform) is also a component of the centrosome and mitotic spindle poles (www.nature.com). Using cell imaging and biochemical fractionation, one study found that BCCIP physically associates with isolated centrosome complexes and localizes around the mother centriole in interphase cells (www.nature.com). As cells enter mitosis, BCCIP disperses from a tight focus at the centriole and spreads into the pericentriolar material at the spindle poles, co-localizing with γ-tubulin and α-tubulin in the mitotic spindle apparatus (www.nature.com). These findings identified BCCIP as a novel component of the microtubule-organizing center in mammalian cells (www.nature.com). Functional experiments have shown that BCCIP is required for proper microtubule organization and spindle integrity. BCCIP can bind directly to tubulin or tubulin-associated structures (demonstrated by co-purification and microtubule pull-down assays) (www.medchemexpress.eu). When BCCIP levels are depleted, cells exhibit pronounced mitotic defects: the mitotic spindles are often disoriented or have abnormal morphology, chromosomes fail to align correctly at the metaphase plate (congression defects), and cells experience delays in mitotic progression (www.nature.com). Furthermore, loss of BCCIP causes issues in microtubule anchoring at the centrosome – for instance, astral microtubules may be unstable or improperly attached, leading to asymmetric or tilted spindles (www.nature.com) (www.nature.com). These phenotypes indicate that BCCIP is necessary for the structural fidelity of the spindle. Notably, the role of BCCIP in mitosis appears to be independent of its DNA repair function (www.nature.com). In BCCIP-depleted cells, the spindle defects are not simply a downstream consequence of DNA damage; instead, BCCIP likely has a direct role in organizing microtubules (possibly by recruiting or stabilizing other centrosomal proteins or motors). BCCIPα might serve as a scaffold at the mother centriole, helping attach centrosomal proteins and anchor microtubules properly (www.nature.com). Consistent with these cellular data, BCCIP knockdown leads to numerical and structural chromosome instability in dividing cells – for example, cells show an increased frequency of lagging chromosomes and chromosome bridges during anaphase, which can arise from the spindle misorganization (journals.plos.org) (www.nature.com). Therefore, BCCIP contributes to genome stability not only by repairing DNA, but also by ensuring accurate chromosome segregation. It acts at the centriole/spindle to maintain mitotic fidelity, thereby preventing aneuploidy and chromosomal mis-segregation events that are often associated with tumorigenesis. Researchers have coined BCCIP as a “centrosomal protein” important for microtubule regulation (www.nature.com), highlighting that its loss leads to defects in spindle architecture and asymmetric cell division. This multi-faceted involvement in both interphase (repair/replication) and mitosis (spindle assembly) underscores BCCIP’s broad role as a caretaker of genome stability.

Role in Ribosome Biogenesis (BCCIPβ Isoform)

An additional, more specialized function of BCCIP was uncovered in the context of ribosome biogenesis. This role is primarily associated with the BCCIPβ isoform. BCCIPβ has a unique C-terminal extension that allows it to interact with components of the 60S ribosomal subunit assembly pathway (pubmed.ncbi.nlm.nih.gov). Specifically, BCCIPβ forms a ternary complex with the ribosomal protein RPL23 (also known as uL14) and the ribosome biogenesis factor eIF6 (pubmed.ncbi.nlm.nih.gov). eIF6 is a nucleolar protein that binds the pre-60S ribosomal subunit and prevents premature association with the 40S subunit; it is required for proper maturation and export of the 60S subunit. The BCCIPβ–RPL23–eIF6 complex is detectable in human cells and depends on the intact BCCIPβ C-terminus (the α isoform, lacking this specific tail sequence, cannot form the same complex) (pubmed.ncbi.nlm.nih.gov). Through this interaction, BCCIPβ appears to act as a nuclear chaperone or escort for RPL23, helping to stabilize RPL23 and incorporate it into assembling 60S ribosomal particles (pubmed.ncbi.nlm.nih.gov). Experimental evidence shows that depletion of BCCIPβ selectively impairs large subunit biogenesis: cells lacking BCCIPβ have reduced levels of free (unassembled) RPL23 and lower amounts of eIF6 in the nucleolus (pubmed.ncbi.nlm.nih.gov). This suggests that without BCCIPβ, RPL23 is less stable or fails to properly localize, and eIF6 cannot be efficiently recruited to nascent ribosomal subunits. Indeed, overexpression of BCCIPβ causes an accumulation of extra-nucleolar RPL23 and prevents its degradation, consistent with BCCIPβ serving as an RPL23-stabilizing factor (pubmed.ncbi.nlm.nih.gov). Follow-up studies (e.g. a 2020 report in Nucleic Acids Research) confirmed that a fraction of mammalian BCCIP (particularly BCCIPβ in human cells) resides in the nucleolus and is critical for 60S ribosome assembly (academic.oup.com) (academic.oup.com). BCCIP was found to be required for the recruitment of eIF6 to the nucleolus and for the normal processing of the 12S pre-rRNA, an early step in large subunit rRNA maturation (academic.oup.com). If BCCIP is knocked down or if its nucleolar localization is disrupted, eIF6 fails to properly localize to nucleoli and 60S subunit production is hindered, leading to defects in ribosome biogenesis and consequent cell proliferation problems (academic.oup.com) (academic.oup.com). Thus, BCCIP (especially BCCIPβ) has an important moonlighting role in the nucleolus: it supports the assembly of ribosomes, which are essential for protein synthesis and cell growth. This finding broadens the scope of BCCIP’s function, showing that its “maintenance of genomic stability” extends to ensuring the protein synthesis machinery is correctly assembled (since impaired ribosome biogenesis can activate p53 and stress pathways). The dual roles of BCCIP isoforms – one in DNA repair/cell cycle and another in ribosome assembly – illustrate how the cell can utilize alternative splicing to adapt a single gene product to multiple crucial pathways.

Biological Significance and Disease Associations

Given its central roles in DNA repair, cell cycle control, and mitotic fidelity, it is not surprising that BCCIP is essential for normal development and that its dysfunction can contribute to diseases such as cancer. Gene knockout studies have shown that BCCIP is indispensable for life: mice completely lacking BCCIP die early in embryogenesis (pubmed.ncbi.nlm.nih.gov). Even partial knockdown of BCCIP in vivo leads to severe defects. For example, conditional BCCIP knockdown in mice causes microcephaly and neural developmental defects, and cells from these mice show proliferation arrest in certain progenitor populations (pmc.ncbi.nlm.nih.gov). Primary cells (mouse embryonic fibroblasts) with experimentally reduced BCCIP levels exhibit pronounced genomic instability, including spontaneously elevated rates of chromosomal breaks and unusual sister chromatid unions (entangled sister chromatids) (journals.plos.org). One study reported a ~3.5-fold increase in chromatid breaks and a 20-fold increase in sister chromatid union events in BCCIP-deficient fibroblasts (journals.plos.org). These aberrations often manifest as chromatin bridges between daughter nuclei during cell division (journals.plos.org). Additionally, BCCIP-deficient cells showed reduced repair of irradiation-induced DNA damage and decreased Rad51 focus formation, reinforcing the idea that BCCIP is required for efficient DNA repair (journals.plos.org). The accumulation of sister chromatid links and anaphase bridges in BCCIP-depleted cells provides a direct mechanistic link to its role in replication stress: it suggests that failure to resolve stalled forks (replication stress) leads to sister chromatid intertwinements that then cause segregation errors in mitosis (journals.plos.org). Taken together, these findings explain why loss of BCCIP causes cell proliferation defects and embryonic lethality – without BCCIP, cells cannot faithfully replicate and segregate their DNA. Consistent with this, knockdown of BCCIP in human cell lines triggers cell cycle arrest or death, indicating that BCCIP is required for cell viability in culture as well (pubmed.ncbi.nlm.nih.gov). Thus, BCCIP qualifies as an essential “caretaker” gene that safeguards genomic stability at multiple levels.

The critical functions of BCCIP in preserving genome integrity imply that its dysregulation can influence cancer development and progression. BCCIP’s locus (10q26) is frequently lost or altered in various cancers, suggesting a potential tumor suppressor role. In astrocytic tumors (brain cancers), for instance, the chromosomal region 10q26 often undergoes loss of heterozygosity (LOH) and this is strongly associated with high-grade, aggressive disease (pmc.ncbi.nlm.nih.gov). Notably, the BCCIP gene resides in this region, and studies have found that BCCIP expression is absent or markedly reduced in a large fraction of astrocytomas. In one analysis of over 100 clinical samples, about 45% of astrocytomas showed no detectable BCCIP protein, and in the most malignant subtype (glioblastoma, grade IV) over 60% of tumors completely lacked BCCIP expression (pmc.ncbi.nlm.nih.gov). This loss of BCCIP was often accompanied by a reduction in BCCIP gene copy number (partial deletion): approximately 45% of glioblastomas had a significant deletion involving the BCCIP locus (pmc.ncbi.nlm.nih.gov). Moreover, there was a clear correlation between low BCCIP levels and tumor aggressiveness (pmc.ncbi.nlm.nih.gov). These data support the notion that BCCIP acts as a tumor suppressor in the context of brain tumors – its loss may enable genomic instability, facilitating tumor initiation or progression. In line with this, the BCCIP protein has been dubbed an “essential caretaker” whose impairment can drive tumorigenesis (pmc.ncbi.nlm.nih.gov). Importantly, BCCIP has not been found to be frequently mutated in cancers; instead, its expression is lost or decreased via copy loss or possibly epigenetic silencing (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This pattern is reminiscent of haploinsufficient tumor suppressors or caretakers that are often downregulated rather than mutated.

Paradoxically, recent studies indicate that BCCIP can also exhibit pro-tumor effects in certain contexts, highlighting a complex, context-dependent role. In some malignancies, cancer cells appear to upregulate BCCIP and depend on its functions for rapid growth. For example, an analysis of lung adenocarcinoma (the most common form of non-small cell lung cancer) found that BCCIP mRNA and protein are significantly overexpressed in tumor tissues compared to normal lung (pubmed.ncbi.nlm.nih.gov). High BCCIP expression in these lung tumors was correlated with poorer patient prognosis – patients with above-median BCCIP levels had significantly shorter survival, as shown by multiple cohort data sets and Kaplan–Meier analyses (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). Functionally, knocking down BCCIP in lung adenocarcinoma cell lines caused a strong G₁/S arrest and inhibited cell proliferation and migration in vitro (pubmed.ncbi.nlm.nih.gov). This suggests that in these cancer cells, BCCIP is required to drive cell cycle progression (perhaps by helping tolerate replication stress or by its role in ribosome biogenesis to support protein synthesis). The same study’s bioinformatic pathway analysis linked BCCIP overexpression to cell cycle and DNA repair gene signatures and found BCCIP levels correlated with markers of immune cell infiltration in the tumor microenvironment (pubmed.ncbi.nlm.nih.gov). The authors concluded that BCCIP acts as an oncogenic factor in lung adenocarcinoma, and they proposed that suppressing BCCIP could be a therapeutic strategy for this cancer subtype (pubmed.ncbi.nlm.nih.gov). How can BCCIP function as a tumor suppressor in some settings and a tumor promoter in others? Insight comes from experimental models and expert analysis. BCCIP’s dual nature may reflect a “Janus” role during tumor evolution. As a genome stability caretaker, BCCIP impairment (partial loss) can initiate tumorigenesis by allowing mutations and karyotypic abnormalities to accumulate (removing the brakes on genomic instability) (pmc.ncbi.nlm.nih.gov). However, complete loss of BCCIP eventually halts proliferation or is lethal to cells, so outright knockout is not often seen in advanced cancers (pubmed.ncbi.nlm.nih.gov). Instead, tumors might start with BCCIP haploinsufficiency to gain mutations, but later they require some BCCIP function for the cancer cells to survive and continue dividing (since rapidly growing tumor cells face replication stress and need ribosome production, both of which require BCCIP) (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In a 2014 study, researchers described a “hit-and-run” scenario for BCCIP in cancer: transient or partial BCCIP downregulation cooperates with p53 loss to trigger tumor formation (initiating oncogenesis through genomic chaos), but then tumors that formed had restored BCCIP levels to support their ongoing growth (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This model aligns with observations in human tumors – some cancers show BCCIP loss (especially early or in less proliferative tumors), whereas others (particularly fast-growing, often p53-deficient tumors) show BCCIP upregulation, presumably to cope with replication stress and high protein synthesis demand. In summary, BCCIP’s role in cancer is context-dependent: it generally behaves as a genome guardian whose loss contributes to tumor initiation, yet cancer cells that do arise may later become reliant on the remaining BCCIP activity for their continued proliferation. This makes BCCIP an interesting potential biomarker or therapeutic target – for instance, restoring BCCIP function might suppress early tumor development in BCCIP-deficient tumors, whereas inhibiting BCCIP could selectively hinder tumors that are “addicted” to its functions (such as certain lung cancers).

Conclusion

In conclusion, BCCIP is a multifaceted protein that underpins genome stability through several complementary mechanisms. It acts in DNA repair (homologous recombination through BRCA2/RAD51 support and replication fork protection), enforces DNA damage checkpoints via p53/p21, contributes to the structural organization of the mitotic spindle for faithful chromosome segregation, and even assists in ribosome biogenesis to meet the protein production needs of the cell. This breadth of function is reflected in its presence in multiple cellular compartments (nucleus, centrosome, nucleolus) and in its evolutionary conservation as an essential gene. Experimentally, BCCIP has been shown to be essential for embryonic development and cellular viability, underscoring its fundamental importance (pubmed.ncbi.nlm.nih.gov). From a clinical perspective, BCCIP emerges as a significant player in cancer biology – its insufficiency can drive genomic instability and tumor initiation, while its continued activity may be exploited by cancer cells for growth. Ongoing research (including structural studies of BCCIP’s domains and interactions (pubmed.ncbi.nlm.nih.gov)) is providing deeper insight into how BCCIP coordinates with its partners (like BRCA2, RAD51, p21, tubulin, and ribosomal proteins) to perform these critical tasks. Understanding BCCIP’s full range of functions and regulation will not only clarify the mechanisms of genome maintenance but could also reveal new opportunities for therapeutic intervention in diseases characterized by genomic instability.

References: The information above is drawn from recent research and reviews, including studies from 2001–2022. Key sources include: functional analyses of BCCIP in DNA repair and cell cycle control (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov), investigations into BCCIP’s role in replication fork protection (FEBS Lett, 2022) (pubmed.ncbi.nlm.nih.gov), cell biology experiments on centrosomal BCCIP in mitosis (Oncogene, 2017) (www.nature.com) (www.nature.com), and studies of BCCIPβ in ribosome biogenesis (FEBS Lett, 2014 (pubmed.ncbi.nlm.nih.gov); Nucleic Acids Res, 2020 (academic.oup.com)). The pathogenic significance of BCCIP is highlighted by cancer genomic studies (e.g., Thoracic Cancer, 2021 (pubmed.ncbi.nlm.nih.gov); Cancer Res, 2009 (pmc.ncbi.nlm.nih.gov)) showing its altered expression in tumors. BCCIP remains an active area of research, as scientists continue to decipher its structure and interactions (pubmed.ncbi.nlm.nih.gov) and evaluate its potential as a genomic stability biomarker or therapeutic target. The consensus from expert analyses is that BCCIP is a critical genome stability factor and a co-factor of major tumor suppressor pathways, whose proper function is indispensable for maintaining cellular and genomic integrity (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).

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  16. AnnotationURLCitation(end_index=4492, start_index=4365, title='BCCIP - BRCA2 and CDKN1A interacting protein Gene | MedChemExpress', type='url_citation', url='https://www.medchemexpress.eu/gene/56647.html#:~:text=mRNA%20%20,interacting%20protein%20isoform%20C')
  17. AnnotationURLCitation(end_index=4797, start_index=4646, title='Structure of human BCCIP and implications for binding and modification of partner proteins - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/33452718/#:~:text=BCCIP%20was%20isolated%20based%20on,two%20crystal%20structures%20of%20an')
  18. AnnotationURLCitation(end_index=5270, start_index=5120, title='BCCIP - BRCA2 and CDKN1A interacting protein Gene | MedChemExpress', type='url_citation', url='https://www.medchemexpress.eu/gene/56647.html#:~:text=This%20gene%20has%205%20transcripts,3%29%20and%2025%20other%20tissues')
  19. AnnotationURLCitation(end_index=5604, start_index=5429, title='BCCIP - BRCA2 and CDKN1A interacting protein Gene | MedChemExpress', type='url_citation', url='https://www.medchemexpress.eu/gene/56647.html#:~:text=This%20gene%20product%20was%20isolated,Multiple%20transcript%20variants%20encoding%20different')
  20. AnnotationURLCitation(end_index=5895, start_index=5770, title='The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC549367/#:~:text=proteins,to%20IR%20and%20sharply%20reduces')
  21. AnnotationURLCitation(end_index=6239, start_index=6093, title='BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis | Nucleic Acids Research | Oxford Academic', type='url_citation', url='https://academic.oup.com/nar/article-abstract/48/22/12817/6007667#:~:text=for%2060S%20ribosome%20biogenesis%20and,Prior%20to')
  22. AnnotationURLCitation(end_index=6533, start_index=6373, title='BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis | Nucleic Acids Research | Oxford Academic', type='url_citation', url='https://academic.oup.com/nar/article-abstract/48/22/12817/6007667#:~:text=ribosome%20subunit%20biogenesis,as%20a%20critical%20factor%20for')
  23. AnnotationURLCitation(end_index=6889, start_index=6717, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=In%20this%20work%20we%20demonstrate,anchoring%2C%20microtubule%20stability%2C%20spindle%20architecture')
  24. AnnotationURLCitation(end_index=7221, start_index=7049, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=In%20this%20work%20we%20demonstrate,anchoring%2C%20microtubule%20stability%2C%20spindle%20architecture')
  25. AnnotationURLCitation(end_index=7343, start_index=7222, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=34,staining%20revealed%20that%20the%20concentration')
  26. AnnotationURLCitation(end_index=7619, start_index=7498, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=34,staining%20revealed%20that%20the%20concentration')
  27. AnnotationURLCitation(end_index=8305, start_index=8159, title='BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15539944/#:~:text=The%20BCCIP%20protein%20is%20a,new%20mechanism%20by%20which%20BCCIP')
  28. AnnotationURLCitation(end_index=8594, start_index=8448, title='BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15539944/#:~:text=The%20BCCIP%20protein%20is%20a,new%20mechanism%20by%20which%20BCCIP')
  29. AnnotationURLCitation(end_index=8901, start_index=8776, title='The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC549367/#:~:text=proteins,to%20IR%20and%20sharply%20reduces')
  30. AnnotationURLCitation(end_index=9495, start_index=9335, title='The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC549367/#:~:text=interference%20markedly%20reduces%20RAD51%20and,to%20DNA%20damage%20and%20HRR')
  31. AnnotationURLCitation(end_index=9827, start_index=9667, title='The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC549367/#:~:text=interference%20markedly%20reduces%20RAD51%20and,to%20DNA%20damage%20and%20HRR')
  32. AnnotationURLCitation(end_index=10222, start_index=10062, title='The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC549367/#:~:text=BCCIP%20reduces%20both%20BRCA2%20and,response%20network%20and%20HRR%20pathway')
  33. AnnotationURLCitation(end_index=10614, start_index=10405, title='Essential Roles of BCCIP in Mouse Embryonic Development and Structural Stability of Chromosomes | PLOS Genetics', type='url_citation', url='https://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1002291#:~:text=MEFs%20displayed%20significant%20spontaneous%20chromosome,damage%2C%20but%20also%20in%20resolving')
  34. AnnotationURLCitation(end_index=11039, start_index=10881, title='The BRCA2 and CDKN1A-interacting protein (BCCIP) stabilizes stalled replication forks and prevents degradation of nascent DNA - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35592921/#:~:text=DNA%20replication%20stress%20is%20characterized,that%20in%20the%20presence%20of')
  35. AnnotationURLCitation(end_index=11365, start_index=11228, title='The BRCA2 and CDKN1A-interacting protein (BCCIP) stabilizes stalled replication forks and prevents degradation of nascent DNA - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35592921/#:~:text=transformation.%20The%20repair,mediated%20degradation%20of')
  36. AnnotationURLCitation(end_index=11792, start_index=11643, title='The BRCA2 and CDKN1A-interacting protein (BCCIP) stabilizes stalled replication forks and prevents degradation of nascent DNA - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35592921/#:~:text=are%20crucial%20for%20protecting%20nascent,mediated%20degradation%20of')
  37. AnnotationURLCitation(end_index=12127, start_index=11972, title='The BRCA2 and CDKN1A-interacting protein (BCCIP) stabilizes stalled replication forks and prevents degradation of nascent DNA - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35592921/#:~:text=BRCA2%20and%20RAD51%20during%20HR,degradation%20of%20nascent%20DNA%20strands')
  38. AnnotationURLCitation(end_index=12413, start_index=12235, title='The BRCA2 and CDKN1A-interacting protein (BCCIP) stabilizes stalled replication forks and prevents degradation of nascent DNA - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35592921/#:~:text=replication%20stress%2C%20BCCIP%20deficiency%20increases,degradation%20of%20nascent%20DNA%20strands')
  39. AnnotationURLCitation(end_index=12797, start_index=12633, title='The BRCA2 and CDKN1A-interacting protein (BCCIP) stabilizes stalled replication forks and prevents degradation of nascent DNA - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35592921/#:~:text=are%20crucial%20for%20protecting%20nascent,degradation%20of%20nascent%20DNA%20strands')
  40. AnnotationURLCitation(end_index=13873, start_index=13727, title='BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15539944/#:~:text=The%20BCCIP%20protein%20is%20a,new%20mechanism%20by%20which%20BCCIP')
  41. AnnotationURLCitation(end_index=14119, start_index=13992, title='CDD Conserved Protein Domain Family: BCCIP', type='url_citation', url='https://www.ncbi.nlm.nih.gov/Structure/cdd/pfam13862#:~:text=CDKN1A,be%20required%20for%20repair%20of')
  42. AnnotationURLCitation(end_index=14505, start_index=14351, title='BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15539944/#:~:text=which%20binds%20to%20a%20highly,which%20BCCIP%20regulates%20p21%20functions')
  43. AnnotationURLCitation(end_index=14824, start_index=14663, title='BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15539944/#:~:text=increases%20p21%20mRNA%20and%20protein,which%20BCCIP%20regulates%20p21%20functions')
  44. AnnotationURLCitation(end_index=15172, start_index=15011, title='BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15539944/#:~:text=increases%20p21%20mRNA%20and%20protein,which%20BCCIP%20regulates%20p21%20functions')
  45. AnnotationURLCitation(end_index=15507, start_index=15341, title='BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15539944/#:~:text=interference%20reduces%20p21%20levels%20and,which%20BCCIP%20regulates%20p21%20functions')
  46. AnnotationURLCitation(end_index=15891, start_index=15725, title='BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15539944/#:~:text=interference%20reduces%20p21%20levels%20and,which%20BCCIP%20regulates%20p21%20functions')
  47. AnnotationURLCitation(end_index=16320, start_index=16151, title='BCCIP - BRCA2 and CDKN1A interacting protein Gene | MedChemExpress', type='url_citation', url='https://www.medchemexpress.eu/gene/56647.html#:~:text=interacting%20domains.%20The%20N,Multiple%20transcript%20variants%20encoding%20different')
  48. AnnotationURLCitation(end_index=16858, start_index=16702, title='BCCIP - BRCA2 and CDKN1A interacting protein Gene | MedChemExpress', type='url_citation', url='https://www.medchemexpress.eu/gene/56647.html#:~:text=This%20gene%20product%20was%20isolated,induced%20homologous%20recombination')
  49. AnnotationURLCitation(end_index=17606, start_index=17434, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=In%20this%20work%20we%20demonstrate,anchoring%2C%20microtubule%20stability%2C%20spindle%20architecture')
  50. AnnotationURLCitation(end_index=17922, start_index=17804, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=BCCIP%20is%20associated%20with%20the,Shown%20are')
  51. AnnotationURLCitation(end_index=18268, start_index=18147, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=34,staining%20revealed%20that%20the%20concentration')
  52. AnnotationURLCitation(end_index=18555, start_index=18383, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=In%20this%20work%20we%20demonstrate,anchoring%2C%20microtubule%20stability%2C%20spindle%20architecture')
  53. AnnotationURLCitation(end_index=18930, start_index=18812, title='BCCIP - BRCA2 and CDKN1A interacting protein Gene | MedChemExpress', type='url_citation', url='https://www.medchemexpress.eu/gene/56647.html#:~:text=enables%20protein%20binding%20%20,GOA')
  54. AnnotationURLCitation(end_index=19332, start_index=19215, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=architecture,utilized%20by%20BCCIP%20in%20tumor')
  55. AnnotationURLCitation(end_index=19706, start_index=19539, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=demonstrate%20BCCIP%2C%20especially%20BCCIP%CE%B1%2C%20as,pole%20to%20ensure%20faithful%20spindle')
  56. AnnotationURLCitation(end_index=19883, start_index=19707, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=new%20component%20of%20the%20centrosome,anchoring%2C%20microtubule%20stability%2C%20spindle%20architecture')
  57. AnnotationURLCitation(end_index=20250, start_index=20074, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=new%20component%20of%20the%20centrosome,anchoring%2C%20microtubule%20stability%2C%20spindle%20architecture')
  58. AnnotationURLCitation(end_index=20796, start_index=20624, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=In%20this%20work%20we%20demonstrate,anchoring%2C%20microtubule%20stability%2C%20spindle%20architecture')
  59. AnnotationURLCitation(end_index=21300, start_index=21091, title='Essential Roles of BCCIP in Mouse Embryonic Development and Structural Stability of Chromosomes | PLOS Genetics', type='url_citation', url='https://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1002291#:~:text=MEFs%20displayed%20significant%20spontaneous%20chromosome,damage%2C%20but%20also%20in%20resolving')
  60. AnnotationURLCitation(end_index=21418, start_index=21301, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=architecture,utilized%20by%20BCCIP%20in%20tumor')
  61. AnnotationURLCitation(end_index=22006, start_index=21830, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=new%20component%20of%20the%20centrosome,anchoring%2C%20microtubule%20stability%2C%20spindle%20architecture')
  62. AnnotationURLCitation(end_index=22750, start_index=22626, title='The beta-isoform of the BRCA2 and CDKN1A(p21)-interacting protein (BCCIP) stabilizes nuclear RPL23/uL14 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25150171/#:~:text=humans,as%20nuclear%20chaperone%20for%20RPL23')
  63. AnnotationURLCitation(end_index=23019, start_index=22895, title='The beta-isoform of the BRCA2 and CDKN1A(p21)-interacting protein (BCCIP) stabilizes nuclear RPL23/uL14 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25150171/#:~:text=humans,as%20nuclear%20chaperone%20for%20RPL23')
  64. AnnotationURLCitation(end_index=23529, start_index=23405, title='The beta-isoform of the BRCA2 and CDKN1A(p21)-interacting protein (BCCIP) stabilizes nuclear RPL23/uL14 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25150171/#:~:text=humans,as%20nuclear%20chaperone%20for%20RPL23')
  65. AnnotationURLCitation(end_index=23878, start_index=23713, title='The beta-isoform of the BRCA2 and CDKN1A(p21)-interacting protein (BCCIP) stabilizes nuclear RPL23/uL14 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25150171/#:~:text=with%20the%20ribosomal%20protein%20RPL23%2FuL14,as%20nuclear%20chaperone%20for%20RPL23')
  66. AnnotationURLCitation(end_index=24260, start_index=24095, title='The beta-isoform of the BRCA2 and CDKN1A(p21)-interacting protein (BCCIP) stabilizes nuclear RPL23/uL14 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25150171/#:~:text=with%20the%20ribosomal%20protein%20RPL23%2FuL14,as%20nuclear%20chaperone%20for%20RPL23')
  67. AnnotationURLCitation(end_index=24756, start_index=24594, title='The beta-isoform of the BRCA2 and CDKN1A(p21)-interacting protein (BCCIP) stabilizes nuclear RPL23/uL14 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25150171/#:~:text=Depletion%20of%20BCCIP%CE%B2%20reduces%20the,as%20nuclear%20chaperone%20for%20RPL23')
  68. AnnotationURLCitation(end_index=25124, start_index=24978, title='BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis | Nucleic Acids Research | Oxford Academic', type='url_citation', url='https://academic.oup.com/nar/article-abstract/48/22/12817/6007667#:~:text=for%2060S%20ribosome%20biogenesis%20and,Prior%20to')
  69. AnnotationURLCitation(end_index=25285, start_index=25125, title='BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis | Nucleic Acids Research | Oxford Academic', type='url_citation', url='https://academic.oup.com/nar/article-abstract/48/22/12817/6007667#:~:text=ribosome%20subunit%20biogenesis,as%20a%20critical%20factor%20for')
  70. AnnotationURLCitation(end_index=25625, start_index=25465, title='BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis | Nucleic Acids Research | Oxford Academic', type='url_citation', url='https://academic.oup.com/nar/article-abstract/48/22/12817/6007667#:~:text=ribosome%20subunit%20biogenesis,as%20a%20critical%20factor%20for')
  71. AnnotationURLCitation(end_index=26033, start_index=25868, title='BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis | Nucleic Acids Research | Oxford Academic', type='url_citation', url='https://academic.oup.com/nar/article-abstract/48/22/12817/6007667#:~:text=arrested%20cell%20growth%20and%20was,to%20the%20nucleolus%20and%2060S')
  72. AnnotationURLCitation(end_index=26180, start_index=26034, title='BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis | Nucleic Acids Research | Oxford Academic', type='url_citation', url='https://academic.oup.com/nar/article-abstract/48/22/12817/6007667#:~:text=for%2060S%20ribosome%20biogenesis%20and,Prior%20to')
  73. AnnotationURLCitation(end_index=27409, start_index=27249, title='Structure of human BCCIP and implications for binding and modification of partner proteins - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/33452718/#:~:text=BCCIP%20was%20isolated%20based%20on,no%20discernible%20sequence%20similarity%20to')
  74. AnnotationURLCitation(end_index=27800, start_index=27669, title='BCCIP Suppresses Tumor Initiation but is Required for Tumor Progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3918420/#:~:text=%2816,we%20showed%20that%20these%20neurogenesis')
  75. AnnotationURLCitation(end_index=28267, start_index=28058, title='Essential Roles of BCCIP in Mouse Embryonic Development and Structural Stability of Chromosomes | PLOS Genetics', type='url_citation', url='https://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1002291#:~:text=MEFs%20displayed%20significant%20spontaneous%20chromosome,damage%2C%20but%20also%20in%20resolving')
  76. AnnotationURLCitation(end_index=28629, start_index=28420, title='Essential Roles of BCCIP in Mouse Embryonic Development and Structural Stability of Chromosomes | PLOS Genetics', type='url_citation', url='https://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1002291#:~:text=MEFs%20displayed%20significant%20spontaneous%20chromosome,damage%2C%20but%20also%20in%20resolving')
  77. AnnotationURLCitation(end_index=28925, start_index=28730, title='Essential Roles of BCCIP in Mouse Embryonic Development and Structural Stability of Chromosomes | PLOS Genetics', type='url_citation', url='https://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1002291#:~:text=breaks.%20Remarkably%2C%20the%20BCCIP,spontaneous%20chromatin%20bridges%20via%20the')
  78. AnnotationURLCitation(end_index=29294, start_index=29125, title='Essential Roles of BCCIP in Mouse Embryonic Development and Structural Stability of Chromosomes | PLOS Genetics', type='url_citation', url='https://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1002291#:~:text=modestly%20at%201,damage%2C%20but%20also%20in%20resolving')
  79. AnnotationURLCitation(end_index=29777, start_index=29617, title='Essential Roles of BCCIP in Mouse Embryonic Development and Structural Stability of Chromosomes | PLOS Genetics', type='url_citation', url='https://journals.plos.org/plosgenetics/article?id=10.1371%2Fjournal.pgen.1002291#:~:text=the%20BCCIP,in%20mitosis%20and%20cell%20division')
  80. AnnotationURLCitation(end_index=30304, start_index=30144, title='Structure of human BCCIP and implications for binding and modification of partner proteins - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/33452718/#:~:text=BCCIP%20was%20isolated%20based%20on,no%20discernible%20sequence%20similarity%20to')
  81. AnnotationURLCitation(end_index=31027, start_index=30878, title='Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2736977/#:~:text=Loss%20of%20heterozygosity%20of%20chromosome,p21%29%20interacting')
  82. AnnotationURLCitation(end_index=31589, start_index=31422, title='Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2736977/#:~:text=We%20found%20that%20BCCIP%20protein,the%20aggressiveness%20of%20astrocytic%20tumors')
  83. AnnotationURLCitation(end_index=31948, start_index=31781, title='Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2736977/#:~:text=We%20found%20that%20BCCIP%20protein,the%20aggressiveness%20of%20astrocytic%20tumors')
  84. AnnotationURLCitation(end_index=32211, start_index=32044, title='Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2736977/#:~:text=We%20found%20that%20BCCIP%20protein,the%20aggressiveness%20of%20astrocytic%20tumors')
  85. AnnotationURLCitation(end_index=32678, start_index=32524, title='BCCIP Suppresses Tumor Initiation but is Required for Tumor Progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3918420/#:~:text=not%20fully%20understood,medulloblastomas%2C%20which%20bear%20a%20wide')
  86. AnnotationURLCitation(end_index=32998, start_index=32847, title='Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2736977/#:~:text=The%20BCCIP%20gene%20is%20located,activity%20of%20wild%20type%20p53')
  87. AnnotationURLCitation(end_index=33130, start_index=32999, title='BCCIP Suppresses Tumor Initiation but is Required for Tumor Progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3918420/#:~:text=%2816,we%20showed%20that%20these%20neurogenesis')
  88. AnnotationURLCitation(end_index=33914, start_index=33750, title='Overexpression of BCCIP predicts an unfavorable prognosis and promotes the proliferation and migration of lung adenocarcinoma - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34297484/#:~:text=Results%3A%20Compared%20with%20normal%20tissue%2C,B%20cell%2C%20macrophage%20and%20DC')
  89. AnnotationURLCitation(end_index=34314, start_index=34150, title='Overexpression of BCCIP predicts an unfavorable prognosis and promotes the proliferation and migration of lung adenocarcinoma - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34297484/#:~:text=Results%3A%20Compared%20with%20normal%20tissue%2C,B%20cell%2C%20macrophage%20and%20DC')
  90. AnnotationURLCitation(end_index=34466, start_index=34315, title='Overexpression of BCCIP predicts an unfavorable prognosis and promotes the proliferation and migration of lung adenocarcinoma - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34297484/#:~:text=BCCIP%20is%20associated%20with%20survival,%28d%29%20Kaplan%E2%80%93Meier')
  91. AnnotationURLCitation(end_index=34788, start_index=34624, title='Overexpression of BCCIP predicts an unfavorable prognosis and promotes the proliferation and migration of lung adenocarcinoma - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34297484/#:~:text=Results%3A%20Compared%20with%20normal%20tissue%2C,B%20cell%2C%20macrophage%20and%20DC')
  92. AnnotationURLCitation(end_index=35348, start_index=35225, title='Overexpression of BCCIP predicts an unfavorable prognosis and promotes the proliferation and migration of lung adenocarcinoma - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34297484/#:~:text=survival,B%20cell%2C%20macrophage%20and%20DC')
  93. AnnotationURLCitation(end_index=35711, start_index=35536, title='Overexpression of BCCIP predicts an unfavorable prognosis and promotes the proliferation and migration of lung adenocarcinoma - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34297484/#:~:text=Conclusions%3A%20Overexpression%20of%20BCCIP%20predicts,prevention%20and%20treatment%20of%20LUAD')
  94. AnnotationURLCitation(end_index=36295, start_index=36144, title='Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2736977/#:~:text=The%20BCCIP%20gene%20is%20located,activity%20of%20wild%20type%20p53')
  95. AnnotationURLCitation(end_index=36602, start_index=36442, title='Structure of human BCCIP and implications for binding and modification of partner proteins - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/33452718/#:~:text=BCCIP%20was%20isolated%20based%20on,no%20discernible%20sequence%20similarity%20to')
  96. AnnotationURLCitation(end_index=37050, start_index=36896, title='BCCIP Suppresses Tumor Initiation but is Required for Tumor Progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3918420/#:~:text=not%20fully%20understood,medulloblastomas%2C%20which%20bear%20a%20wide')
  97. AnnotationURLCitation(end_index=37200, start_index=37051, title='BCCIP Suppresses Tumor Initiation but is Required for Tumor Progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3918420/#:~:text=restored%20in%20the%20tumor%20tissues,lane%202%20of%20Figure%205A')
  98. AnnotationURLCitation(end_index=37673, start_index=37519, title='BCCIP Suppresses Tumor Initiation but is Required for Tumor Progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3918420/#:~:text=not%20fully%20understood,medulloblastomas%2C%20which%20bear%20a%20wide')
  99. AnnotationURLCitation(end_index=37823, start_index=37674, title='BCCIP Suppresses Tumor Initiation but is Required for Tumor Progression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC3918420/#:~:text=restored%20in%20the%20tumor%20tissues,lane%202%20of%20Figure%205A')
  100. AnnotationURLCitation(end_index=39688, start_index=39528, title='Structure of human BCCIP and implications for binding and modification of partner proteins - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/33452718/#:~:text=BCCIP%20was%20isolated%20based%20on,no%20discernible%20sequence%20similarity%20to')
  101. AnnotationURLCitation(end_index=40155, start_index=40004, title='Structure of human BCCIP and implications for binding and modification of partner proteins - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/33452718/#:~:text=BCCIP%20was%20isolated%20based%20on,two%20crystal%20structures%20of%20an')
  102. AnnotationURLCitation(end_index=40923, start_index=40763, title='The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC549367/#:~:text=interference%20markedly%20reduces%20RAD51%20and,to%20DNA%20damage%20and%20HRR')
  103. AnnotationURLCitation(end_index=41085, start_index=40924, title='BCCIP functions through p53 to regulate the expression of p21Waf1/Cip1 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/15539944/#:~:text=increases%20p21%20mRNA%20and%20protein,which%20BCCIP%20regulates%20p21%20functions')
  104. AnnotationURLCitation(end_index=41333, start_index=41169, title='The BRCA2 and CDKN1A-interacting protein (BCCIP) stabilizes stalled replication forks and prevents degradation of nascent DNA - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/35592921/#:~:text=are%20crucial%20for%20protecting%20nascent,degradation%20of%20nascent%20DNA%20strands')
  105. AnnotationURLCitation(end_index=41581, start_index=41409, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=In%20this%20work%20we%20demonstrate,anchoring%2C%20microtubule%20stability%2C%20spindle%20architecture')
  106. AnnotationURLCitation(end_index=41699, start_index=41582, title='Regulation of spindle integrity and mitotic fidelity by BCCIP | Oncogene', type='url_citation', url='https://www.nature.com/articles/onc201792#:~:text=architecture,utilized%20by%20BCCIP%20in%20tumor')
  107. AnnotationURLCitation(end_index=41887, start_index=41763, title='The beta-isoform of the BRCA2 and CDKN1A(p21)-interacting protein (BCCIP) stabilizes nuclear RPL23/uL14 - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/25150171/#:~:text=humans,as%20nuclear%20chaperone%20for%20RPL23')
  108. AnnotationURLCitation(end_index=42073, start_index=41913, title='BCCIP is required for nucleolar recruitment of eIF6 and 12S pre-rRNA production during 60S ribosome biogenesis | Nucleic Acids Research | Oxford Academic', type='url_citation', url='https://academic.oup.com/nar/article-abstract/48/22/12817/6007667#:~:text=ribosome%20subunit%20biogenesis,as%20a%20critical%20factor%20for')
  109. AnnotationURLCitation(end_index=42347, start_index=42183, title='Overexpression of BCCIP predicts an unfavorable prognosis and promotes the proliferation and migration of lung adenocarcinoma - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/34297484/#:~:text=Results%3A%20Compared%20with%20normal%20tissue%2C,B%20cell%2C%20macrophage%20and%20DC')
  110. AnnotationURLCitation(end_index=42533, start_index=42366, title='Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2736977/#:~:text=We%20found%20that%20BCCIP%20protein,the%20aggressiveness%20of%20astrocytic%20tumors')
  111. AnnotationURLCitation(end_index=42836, start_index=42685, title='Structure of human BCCIP and implications for binding and modification of partner proteins - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/33452718/#:~:text=BCCIP%20was%20isolated%20based%20on,two%20crystal%20structures%20of%20an')
  112. AnnotationURLCitation(end_index=43313, start_index=43153, title='The BRCA2-Interacting Protein BCCIP Functions in RAD51 and BRCA2 Focus Formation and Homologous Recombinational Repair - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC549367/#:~:text=BCCIP%20reduces%20both%20BRCA2%20and,response%20network%20and%20HRR%20pathway')
  113. AnnotationURLCitation(end_index=43465, start_index=43314, title='Alterations of BCCIP, a BRCA2 interacting protein, in astrocytomas - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC2736977/#:~:text=The%20BCCIP%20gene%20is%20located,activity%20of%20wild%20type%20p53')