DOT1

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005634 nucleus	IBA GO_REF:0000033	ACCEPT	Summary: DOT1 localizes to the nucleus where it performs its enzymatic functions on chromatin. IBA evidence from phylogenetic analysis is appropriate for this well-conserved component localization. Reason: Nuclear localization is well-established and core to DOT1 function. Contains multiple NLS signals. IBA annotation based on ortholog conservation is appropriate. Supporting Evidence: file:yeast/DOT1/DOT1-deep-research-perplexity.md provider: perplexity
GO:0031151 histone H3K79 methyltransferase activity	IBA GO_REF:0000033	ACCEPT	Summary: DOT1's primary molecular function is H3K79 methyltransferase activity, the founding member of this enzyme class. IBA evidence reflects strong ortholog conservation across eukaryotes. Cryo-EM structures of yeast Dot1 bound to the nucleosome with the SAM cofactor (PDB 7K6P and 7K6Q; Valencia-Sanchez et al. 2021) directly visualize the catalytic engagement of H3K79 in the Dot1 active site, confirming this molecular function structurally. Reason: This is the core enzymatic activity of DOT1. H3K79 methylation requires nucleosomal context and is not processive. IBA annotation appropriately reflects the highly conserved nature of this specific function across eukaryotes. Supporting Evidence: file:yeast/DOT1/DOT1-deep-research-falcon.md Dot1p is a non-SET, SAM-dependent methyltransferase that methylates H3K79 specifically on nucleosomes/chromatin (not free histones), producing mono-, di-, and tri-methylation states via a distributive (non-processive) mechanism. PMID:33479126 The conserved factor Dot1 (disruptor of telomeric silencing-1) is the only known methyltransferase that catalyzes mono-, di-, and trimethylation of H3K79 (H3K79me1, -me2, and -me3) PMID:33479126 The structure revealed Dot1 (residues 176 to 580) bound to the nucleosome in a catalytic conformation
GO:0031509 subtelomeric heterochromatin formation	IBA GO_REF:0000033	ACCEPT	Summary: DOT1 promotes subtelomeric heterochromatin formation indirectly by preventing Sir protein mislocalization through H3K79 methylation, creating an inhospitable chromatin environment for repressive proteins. Reason: While DOT1 itself marks active chromatin with H3K79 methylation, loss of DOT1 causes Sir protein spreading and derepression of subtelomeric regions. This represents an important function that is conserved across organisms with similar chromatin structure. IBA annotation reflects functional conservation. Supporting Evidence: file:yeast/DOT1/DOT1-deep-research-falcon.md Dot1p was originally identified through effects on telomeric silencing, and mechanistically H3K79 methylation antagonizes Sir3 binding and Sir complex localization/spreading. Dot1 deletion or H3K79 mutation compromises telomeric silencing and alters Sir protein localization
GO:0006281 DNA repair	IBA GO_REF:0000033	ACCEPT	Summary: DOT1-mediated H3K79 methylation plays multiple roles in DNA damage repair through enabling checkpoint signaling and facilitating recruitment of repair factors to damage sites. Reason: H3K79 methylation is required for efficient DNA repair through multiple pathways including homologous recombination, nucleotide excision repair, and translesion synthesis regulation. This function is conserved across eukaryotes as evidenced by DOT1L's role in mammalian DNA damage responses. IBA annotation appropriately reflects this conservation.
GO:0000077 DNA damage checkpoint signaling	IBA GO_REF:0000033	ACCEPT	Summary: DOT1-mediated H3K79 methylation is essential for DNA damage checkpoint control, enabling recruitment of the Rad9/53BP1 checkpoint protein via methyl-lysine reader domains. Reason: H3K79 methylation is a key signal that enables recruitment of the Rad9 checkpoint protein (through its tudor domain) to double-strand breaks. This mechanism is conserved between yeast Rad9 and human 53BP1. DOT1 mutants show severe checkpoint defects. IBA annotation reflects strong functional conservation. Supporting Evidence: file:yeast/DOT1/DOT1-deep-research-falcon.md Dot1/H3K79 methylation contributes to genome stability and DNA damage checkpoint signaling. Defects in Dot1/H3K79 methylation can impair recruitment of DNA damage response factors and checkpoint activation (e.g., G1 and intra-S checkpoint defects described in yeast contexts)
GO:0000077 DNA damage checkpoint signaling	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based IEA annotation recognizing DOT1 as a methyltransferase involved in DNA damage checkpoint control. Reason: While the annotation is correct, it is a computational inference from InterPro domain annotation rather than direct evidence. The experimental evidence (IBA and IMP) for this function is superior and this IEA annotation is superseded by stronger evidence.
GO:0000781 chromosome, telomeric region	IEA GO_REF:0000108	MODIFY	Summary: DOT1 localizes to telomeric and subtelomeric regions where it influences heterochromatin formation and silencing dynamics. Reason: While DOT1 does localize to telomeric chromatin and affects telomeric silencing, calling it 'located_in' the telomeric region may be misleading. DOT1 is primarily a global histone methyltransferase found throughout the nucleus and euchromatic regions, with particular functional importance at telomeres. The annotation should more precisely characterize as involvement in telomeric heterochromatin rather than constitutive localization. Proposed replacements: nucleus
GO:0000786 nucleosome	IEA GO_REF:0000002	ACCEPT	Summary: DOT1 binds to nucleosomes and catalyzes methylation exclusively in nucleosomal context, showing strong substrate preference for nucleosomal over free histones. Reason: This annotation correctly reflects DOT1's essential interaction with nucleosomes. DOT1 has essentially no activity on free histone H3, requiring the nucleosomal context for both binding and catalytic activity. Supporting Evidence: file:yeast/DOT1/DOT1-deep-research-falcon.md A central defining feature is that Dot1p is nucleosome/chromatin dependent and does not efficiently methylate free histone H3/free histones; thus, the physiologically relevant substrate is nucleosomal H3K79 within chromatin.
GO:0003677 DNA binding	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: DOT1 has been shown to bind DNA in vitro, though the functional significance of this DNA binding activity in vivo remains unclear. Reason: UniProt annotation indicates DOT1 can bind DNA but the physiological relevance is uncertain. The primary function is histone methylation on nucleosomal substrates. The annotation is technically correct but represents a secondary property.
GO:0005634 nucleus	IEA GO_REF:0000120	ACCEPT	Summary: Computational annotation of nuclear localization based on UniProtKB subcellular location annotation. Reason: This is a redundant annotation with the IBA GO:0005634 annotation but both provide complementary evidence from different sources. The IBA version is more reliable but this IEA annotation provides additional computational support.
GO:0006281 DNA repair	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based annotation recognizing DOT1's role in DNA repair. Reason: Redundant with the IBA GO:0006281 annotation. Both are correct and provide complementary evidence. InterPro domain-based inference provides additional computational support.
GO:0006325 chromatin organization	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: DOT1-mediated H3K79 methylation is part of chromatin organization through mark deposition and modulation of Sir protein distribution. Reason: This is a broad, general annotation that is correct but captures a secondary consequence of DOT1 activity. The core function is H3K79 methylation with specific roles in checkpoint signaling and heterochromatin boundary formation. More specific annotations better capture DOT1's function.
GO:0006351 DNA-templated transcription	IEA GO_REF:0000043	KEEP AS NON CORE	Summary: H3K79 methylation by DOT1 marks and supports active transcription, with enrichment in gene bodies of transcribed genes. Reason: DOT1 does contribute to transcriptional regulation, but the primary function is histone methylation that indirectly supports transcription through preventing heterochromatin spreading and marking active chromatin. More specific process annotations better capture DOT1's specific roles. Falcon deep research confirms H3K79 methylation correlates strongly with transcriptional activity and is enriched in transcribed (gene body) regions, with H2Bub1 coupling Dot1 to elongating RNA polymerase II via the Paf1 complex. Supporting Evidence: file:yeast/DOT1/DOT1-deep-research-falcon.md H3K79 methylation correlates strongly with transcriptional activity and is enriched in transcribed regions, consistent with Dot1 acting in euchromatin and being regulated by elongation-associated histone crosstalk (H2Bub1).
GO:0008168 methyltransferase activity	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: DOT1 exhibits broad methyltransferase activity, specifically acting as an H3K79 methyltransferase. This annotation is correct but overly general. Reason: While technically correct, this is an overly broad term that obscures the specific substrate and lysine residue (H3K79). The specific term GO:0031151 'histone H3K79 methyltransferase activity' is much more informative and already annotated. This general term provides no additional functional information.
GO:0016740 transferase activity	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: DOT1 transfers methyl groups from SAM to histone H3 lysine-79, making it a transferase. Reason: This is an excessively broad parent term that is technically correct but provides minimal functional information. DOT1 is specifically a methyltransferase (GO:0008168) acting on H3K79 (GO:0031151). These more specific terms already capture the functional information.
GO:0031151 histone H3K79 methyltransferase activity	IEA GO_REF:0000002	ACCEPT	Summary: InterPro domain-based annotation of DOT1's specific H3K79 methyltransferase activity, the core enzymatic function. Reason: This is the most specific and informative molecular function annotation. InterPro domain signatures correctly predict this activity. Redundant with IBA and IDA annotations but all three levels of evidence support this core function.
GO:0031509 subtelomeric heterochromatin formation	IEA GO_REF:0000002	ACCEPT	Summary: InterPro-based annotation recognizing DOT1's role in subtelomeric heterochromatin formation. Reason: Redundant with IBA and IMP annotations for the same term. All provide complementary evidence from different sources. InterPro domain-based inference provides additional computational support.
GO:0032259 methylation	IEA GO_REF:0000043	MARK AS OVER ANNOTATED	Summary: DOT1 catalyzes histone H3K79 methylation, placing it in the broader methylation process category. Reason: This is overly broad. GO:0032259 'methylation' is a very general term that could apply to any methylation event in the cell. More specific process terms are available: GO:0031151 for the molecular function and GO:0031509 or checkpoint-related terms for biological processes.
GO:0042393 histone binding	IEA GO_REF:0000002	ACCEPT	Summary: DOT1 binds to histones (particularly H3 and H4) as part of nucleosome recognition and catalysis. Reason: DOT1 forms extensive contacts with histones during nucleosome binding and catalysis, particularly with the histone H4 tail basic patch region. This annotation correctly describes a required molecular interaction for enzyme function. Falcon deep research provides quantitative nucleosome-binding affinities (Kd ~70-83 nM) consistent with direct, stable histone/nucleosome engagement. Supporting Evidence: file:yeast/DOT1/DOT1-deep-research-falcon.md Dot1 binds unmodified vs H4K16ac nucleosomes with similar Kd values:
GO:0051726 regulation of cell cycle	IEA GO_REF:0000002	KEEP AS NON CORE	Summary: DOT1's role in DNA damage checkpoints (both G1 and intra-S phase) indirectly regulates cell cycle progression by preventing progression through checkpoints when DNA damage is present. Reason: While DOT1 does affect cell cycle through its checkpoint functions, calling this 'regulation of cell cycle' is misleading. DOT1 specifically regulates checkpoint control (GO:0000077, GO:0031571, GO:0031573) not the cell cycle per se. The checkpoint terms are more precise.
GO:0140956 histone H3K79 trimethyltransferase activity	IEA GO_REF:0000120	ACCEPT	Summary: DOT1 catalyzes all three methylation states at H3K79 (me1, me2, me3) through distributive sequential catalysis. The trimethylation is catalytically distinct from monomethylation. Reason: DOT1 does catalyze H3K79 trimethylation as one of three possible methylation states. While most H3K79 is monomethylated in vivo, the trimethylation activity is documented and has specific roles at centromeres during meiosis and marking active transcription. Falcon deep research notes that efficient di-/trimethylation depends on prior H2B-K123 monoubiquitination and is allosterically stimulated by H4K16 acetylation, which increase catalytic turnover toward the higher methylation states. Supporting Evidence: file:yeast/DOT1/DOT1-deep-research-falcon.md H2B-K123 monoubiquitination (H2Bub1) stimulates Dot1-dependent H3K79 methylation, especially higher methylation states (di-/tri-methylation).
GO:0005515 protein binding	IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom...	REMOVE	Summary: DOT1 has multiple protein-protein interactions documented in IntAct database from high-throughput yeast two-hybrid and biochemical studies. Reason: While the annotation is technically supported by IPI evidence, 'protein binding' is excessively uninformative. It tells us nothing about which proteins, what the functional relevance is, or what the biological consequence is. This violates curation guidelines to avoid vague terms like 'protein binding'. Specific protein-protein interactions should be captured through more specific functional annotations. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae.
GO:0031509 subtelomeric heterochromatin formation	IMP PMID:11029058 Role for the silencing protein Dot1 in meiotic checkpoint co...	ACCEPT	Summary: Direct experimental evidence (IMP) showing DOT1 is essential for proper subtelomeric heterochromatin formation and maintenance. Reason: DOT1 deletion mutants show mislocalization of Sir proteins and loss of subtelomeric heterochromatin. Loss of Dot1 allows Sir proteins to spread into normally transcribed regions. This is a well-characterized core function with strong genetic evidence. Supporting Evidence: PMID:11029058 Role for the silencing protein Dot1 in meiotic checkpoint control.
GO:0031571 mitotic G1 DNA damage checkpoint signaling	IMP PMID:16166626 Role of Dot1-dependent histone H3 methylation in G1 and S ph...	ACCEPT	Summary: Direct mutant phenotype evidence showing DOT1-dependent H3K79 methylation is required for G1 checkpoint arrest in response to DNA damage. Reason: DOT1 deletion mutants fail to arrest at the G1 checkpoint when treated with ionizing radiation. Catalytically inactive dot1 mutants cannot restore checkpoint function. H3K79R histone mutants also show checkpoint defects. This is a core DOT1 function with strong experimental evidence. Supporting Evidence: PMID:16166626 Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9.
GO:0031509 subtelomeric heterochromatin formation	IMP PMID:26587833 Competition between Heterochromatic Loci Allows the Abundanc...	ACCEPT	Summary: Redundant IMP annotation for subtelomeric heterochromatin formation from independent research source. Reason: Multiple independent studies demonstrate DOT1's essential role in subtelomeric heterochromatin formation. Having multiple references for the same annotation with IMP evidence strengthens confidence in this core function. Supporting Evidence: PMID:26587833 eCollection 2015 Nov.
GO:0006334 nucleosome assembly	IDA PMID:29339748 Dot1 regulates nucleosome dynamics by its inherent histone c...	KEEP AS NON CORE	Summary: Direct observation evidence showing DOT1 has histone chaperone activity that regulates nucleosome dynamics independent of methylation. Reason: DOT1 has methylation-independent histone chaperone function that affects nucleosome assembly and dynamics. While correct, this is a secondary function. DOT1's primary roles are H3K79 methylation, checkpoint signaling, and heterochromatin boundary formation. Falcon deep research corroborates this with mechanistic detail: Dot1p can assemble core histones into nucleosomes and facilitate ATP-dependent remodeling in vitro, a nucleosome-binding domain (residues 101-140) is required, and catalytically inactive mutants still stimulate remodeling, confirming the activity is methylation-independent. Supporting Evidence: PMID:29339748 Dot1 regulates nucleosome dynamics by its inherent histone chaperone activity in yeast. file:yeast/DOT1/DOT1-deep-research-falcon.md A major yeast-specific advance is evidence that Dot1p has intrinsic histone chaperone activity that regulates nucleosome dynamics and histone exchange independently of methyltransferase activity file:yeast/DOT1/DOT1-deep-research-falcon.md Catalytically inactive Dot1 mutants can still stimulate remodeling, supporting methylation-independent function.
GO:0031452 negative regulation of heterochromatin formation	IMP PMID:26587833 Competition between Heterochromatic Loci Allows the Abundanc...	ACCEPT	Summary: DOT1-mediated H3K79 methylation prevents or antagonizes heterochromatin formation by creating chromatin that is incompatible with Sir protein binding and function. Reason: By depositing H3K79 methylation marks in euchromatin, DOT1 prevents ectopic heterochromatin assembly. Loss of DOT1 allows Sir protein spreading. This represents an important negative feedback mechanism that maintains chromatin domain boundaries. Supporting Evidence: PMID:26587833 eCollection 2015 Nov. file:yeast/DOT1/DOT1-deep-research-falcon.md Dot1 overexpression can spread H3K79 methylation into normally silent chromatin and displace Sir proteins.
GO:0000077 DNA damage checkpoint signaling	IMP PMID:17267293 Methylation of histone H3 lysine-79 by Dot1p plays multiple ...	ACCEPT	Summary: Direct mutant phenotype evidence showing DOT1-dependent H3K79 methylation is required for DNA damage checkpoint signaling in response to multiple DNA damage types. Reason: DOT1 deletion results in defects in checkpoint response to ionizing radiation and UV damage. This is a core, well-established function with strong mutant phenotype evidence. Supporting Evidence: PMID:17267293 Epub 2007 Jan 30. Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae.
GO:0000077 DNA damage checkpoint signaling	IGI PMID:17267293 Methylation of histone H3 lysine-79 by Dot1p plays multiple ...	ACCEPT	Summary: Interaction-based evidence showing DOT1 functions in the DNA damage checkpoint signaling pathway in concert with other factors including Rad9. Reason: IGI evidence shows DOT1 functions in genetic interaction with known checkpoint proteins. Epistasis analysis demonstrates DOT1 is part of the checkpoint signaling pathway. Complementary to IMP evidence and provides pathway context. Supporting Evidence: PMID:17267293 Epub 2007 Jan 30. Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae.
GO:0000725 recombinational repair	IMP PMID:17267293 Methylation of histone H3 lysine-79 by Dot1p plays multiple ...	ACCEPT	Summary: Direct evidence showing DOT1-mediated H3K79 methylation is required for efficient homologous recombination repair of DNA damage. Reason: DOT1 plays a critical role in promoting homologous recombination repair of double-strand breaks. Loss of DOT1 reduces HR efficiency. This is a specific DNA repair pathway function with strong experimental evidence. Supporting Evidence: PMID:17267293 Epub 2007 Jan 30. Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae.
GO:0000725 recombinational repair	IGI PMID:17267293 Methylation of histone H3 lysine-79 by Dot1p plays multiple ...	ACCEPT	Summary: Genetic interaction evidence showing DOT1 functions with other recombinational repair factors in a common pathway. Reason: IGI evidence complements IMP by showing DOT1's epistatic relationships with recombination repair genes. This provides pathway context for DOT1's role. Supporting Evidence: PMID:17267293 Epub 2007 Jan 30. Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae.
GO:0005634 nucleus	IDA PMID:11029058 Role for the silencing protein Dot1 in meiotic checkpoint co...	ACCEPT	Summary: Direct observation evidence of DOT1 nuclear localization from immunolocalization studies. Reason: Direct experimental observation of nuclear localization. IDA evidence is strong for localization. Complementary to IBA and IEA annotations for the same localization. Supporting Evidence: PMID:11029058 Role for the silencing protein Dot1 in meiotic checkpoint control. file:yeast/DOT1/DOT1-deep-research-falcon.md Functionally, Dot1 is nuclear/chromatin-associated, acting on nucleosomes across euchromatic transcribed regions and at boundaries of silent chromatin such as telomeres.
GO:0006289 nucleotide-excision repair	IMP PMID:17267293 Methylation of histone H3 lysine-79 by Dot1p plays multiple ...	ACCEPT	Summary: Direct evidence showing DOT1-mediated H3K79 methylation supports nucleotide excision repair pathway for UV damage repair. Reason: DOT1 deletion results in hypersensitivity to UV damage and reduced NER efficiency. H3K79 methylation facilitates recruitment of NER factors to damage sites. This is a specific DNA repair pathway function with solid experimental evidence. Supporting Evidence: PMID:17267293 Epub 2007 Jan 30. Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae.
GO:0006289 nucleotide-excision repair	IGI PMID:17267293 Methylation of histone H3 lysine-79 by Dot1p plays multiple ...	ACCEPT	Summary: Genetic interaction evidence showing DOT1's functional relationships with NER pathway genes. Reason: IGI evidence provides pathway context, showing DOT1 functions with NER genes in common pathways. Complementary to IMP evidence. Supporting Evidence: PMID:17267293 Epub 2007 Jan 30. Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae.
GO:0006301 DNA damage tolerance	IGI PMID:17267293 Methylation of histone H3 lysine-79 by Dot1p plays multiple ...	ACCEPT	Summary: Genetic interaction evidence showing DOT1 is involved in regulating DNA damage tolerance through translesion synthesis pathways to maintain genome integrity. Reason: DOT1 negatively regulates translesion synthesis (TLS), an error-prone repair pathway. This prevents accumulation of mutations by suppressing mutagenic repair mechanisms when high-fidelity repair is available. IGI evidence is appropriate for this pathway function. Supporting Evidence: PMID:17267293 Epub 2007 Jan 30. Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae.
GO:0031151 histone H3K79 methyltransferase activity	IDA PMID:12080090 Lysine methylation within the globular domain of histone H3 ...	ACCEPT	Summary: Direct observation evidence from biochemical assays showing DOT1 catalyzes H3K79 methylation. The cryo-EM structures of yeast Dot1 bound to the nucleosome with bound SAM cofactor (PDB 7K6P and 7K6Q; Valencia-Sanchez et al. 2021) show H3K79 inserted into the hydrophobic Dot1 active site adjacent to the SAM methyl donor, providing a structural basis for this catalytic activity. Reason: Direct biochemical demonstration of DOT1's methyltransferase activity on histone H3K79. IDA evidence from enzymatic assays is the strongest form of evidence for enzyme function. Supporting Evidence: PMID:12080090 Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. file:yeast/DOT1/DOT1-deep-research-falcon.md Dot1 transfers methyl groups from S-adenosyl-L-methionine (SAM/AdoMet) to histone H3 Lys79, generating H3K79me1, H3K79me2, and H3K79me3 PMID:33479126 The active site of Dot1 consists of hydrophobic and aromatic residues of Dot1, cofactor S-adenosyl methionine (SAM), and residues of the H4 amino tail PMID:33479126 H3K79 is inserted into the hydrophobic active site and anchored through van der Waals interactions
GO:0031151 histone H3K79 methyltransferase activity	IMP PMID:12080090 Lysine methylation within the globular domain of histone H3 ...	ACCEPT	Summary: Mutant phenotype evidence showing DOT1 catalytic mutations abolish H3K79 methyltransferase function and cause observable phenotypes. Reason: Catalytically inactive dot1 mutants fail to methylate H3K79 and show checkpoint defects. This provides independent confirmation of DOT1's methyltransferase role. IMP evidence complements IDA evidence. Supporting Evidence: PMID:12080090 Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association.
GO:0031151 histone H3K79 methyltransferase activity	IDA PMID:18158898 Interplay of chromatin modifiers on a short basic patch of h...	ACCEPT	Summary: Direct observation evidence from additional source further demonstrating H3K79 methyltransferase activity. Reason: Multiple independent studies confirm DOT1's H3K79 methyltransferase activity through direct biochemical observation. Multiple IDA sources provide high confidence in this core molecular function. Supporting Evidence: PMID:18158898 Interplay of chromatin modifiers on a short basic patch of histone H4 tail defines the boundary of telomeric heterochromatin.
GO:0031573 mitotic intra-S DNA damage checkpoint signaling	IMP PMID:16166626 Role of Dot1-dependent histone H3 methylation in G1 and S ph...	ACCEPT	Summary: Direct mutant phenotype evidence showing DOT1-dependent H3K79 methylation is required for intra-S phase checkpoint control. Reason: DOT1 is required for the intra-S DNA damage checkpoint that prevents DNA replication when damage is present. DOT1 deletion mutants fail to slow replication upon DNA damage. This is a distinct checkpoint pathway and DOT1 is essential for both G1 and intra-S checkpoints. Supporting Evidence: PMID:16166626 Role of Dot1-dependent histone H3 methylation in G1 and S phase DNA damage checkpoint functions of Rad9.
GO:0051598 meiotic recombination checkpoint signaling	IGI PMID:11029058 Role for the silencing protein Dot1 in meiotic checkpoint co...	ACCEPT	Summary: Genetic interaction evidence showing DOT1 functions in the pachytene meiotic checkpoint that monitors proper chromosome synapsis and recombination. Reason: The pachytene checkpoint prevents progression through meiotic prophase I when chromosome synapsis or recombination is defective. DOT1 mutants fail to arrest meiosis despite synapsis/recombination defects. This is a critical meiotic function with clear genetic evidence. Supporting Evidence: PMID:11029058 Role for the silencing protein Dot1 in meiotic checkpoint control.
GO:0070911 global genome nucleotide-excision repair	IMP PMID:21460225 Evidence that the histone methyltransferase Dot1 mediates gl...	ACCEPT	Summary: Direct evidence showing DOT1-mediated H3K79 methylation is involved in the global genome nucleotide excision repair pathway, distinct from transcription-coupled NER. Reason: DOT1 specifically contributes to GG-NER, the pathway that scans the entire genome for lesions independent of transcription. This is a specialized NER pathway function with experimental support from mutant phenotype analysis. Supporting Evidence: PMID:21460225 2011 Apr 1. Evidence that the histone methyltransferase Dot1 mediates global genomic repair by methylating histone H3 on lysine 79.
GO:0006357 regulation of transcription by RNA polymerase II	NAS	NEW	Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations.
GO:0006974 DNA damage response	NAS	NEW	Summary: Added to align core_functions with existing annotations. Reason: Core function term not present in existing_annotations.

Gene Description

Existing Annotations Review

Core Functions

References

Deep Research

Falcon

Perplexity

📚 Additional Documentation

Curation Summary

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