| Topic | Key findings | Evidence type (worm primary vs cross-species review/structural) | Best supporting sources (authors, year, URL) | Citation IDs to use |
|---|---|---|---|---|
| Identity / synonyms | The target is **Caenorhabditis elegans mcm-4**, historically identified as **lin-6**; primary worm literature states that **lin-6 corresponds to mcm-4** and encodes the **single C. elegans MCM-4 subunit** of the **MCM2-7 replicative helicase / replication licensing machinery**. UniProt-provided synonyms also include **let-358**; this synonym was not explicitly recovered in the retrieved papers, so it should be treated as database-supported rather than paper-verified here. | Worm primary + database-context alignment | Korzelius et al., 2011, https://doi.org/10.1016/j.ydbio.2010.12.009; Ruijtenberg et al., 2011, https://doi.org/10.5772/19397 | (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000003) |
| Molecular function | MCM-4 functions as one subunit of the **AAA+ ATPase MCM2-7 heterohexamer**, the core of the eukaryotic replicative helicase. In active form, **CMG (Cdc45-MCM2-7-GINS)** uses ATP hydrolysis to unwind parental duplex DNA by **steric exclusion** while translocating **3'→5' on the leading-strand ssDNA**. Substrate context: dsDNA at licensed origins is converted to ssDNA templates for replication forks; MCM4 contributes to this complex activity rather than acting as a known standalone enzyme in worms. | Cross-species review/structural, used to infer precise biochemistry for worm ortholog | You & Masai, 2024, https://doi.org/10.3390/biology13080629; Xu et al., 2023, https://doi.org/10.1038/s41467-023-41506-0; Xiang et al., 2023, https://doi.org/10.1038/s41388-022-02572-8 | (pqac-00000007, pqac-00000008, pqac-00000010, pqac-00000012, pqac-00000014) |
| Biological processes / pathways | Core role in **replication licensing**, **origin firing**, **S-phase progression**, and the **replication checkpoint**. In worms, mcm-4 is required for productive DNA synthesis and contributes to checkpoint-dependent delay of mitosis under replication stress; it acts in the conserved pathway with **ORC, CDC-6, CDT-1**, and downstream **CMG** assembly/activation factors. | Worm primary with mechanistic support from reviews | Korzelius et al., 2011, https://doi.org/10.1016/j.ydbio.2010.12.009; Sonneville et al., 2012, https://doi.org/10.1083/jcb.201110080; Gaggioli et al., 2014, https://doi.org/10.1083/jcb.201310083; You & Masai, 2024, https://doi.org/10.3390/biology13080629 | (pqac-00000015, pqac-00000017, pqac-00000019, pqac-00000022, pqac-00000026, pqac-00000029) |
| Localization / dynamics | In C. elegans, MCM-4 is **nuclear during interphase**, **diffuse / not chromosome-associated in metaphase**, and **re-associates with chromatin in late anaphase**, matching licensing at mitotic exit. Related worm imaging of MCM2-7 shows loading in **late M / early G1**, with a large soluble nuclear pool in interphase and pre-RC dependence on **cdc-6/cdt-1/orc-5**. | Worm primary | Korzelius et al., 2011, https://doi.org/10.1016/j.ydbio.2010.12.009; Sonneville et al., 2012, https://doi.org/10.1083/jcb.201110080; Sonneville et al., 2015, https://doi.org/10.1016/j.celrep.2015.06.046 | (pqac-00000022, pqac-00000023, pqac-00000024, pqac-00000025, pqac-00000027, pqac-00000028) |
| Key phenotypes | Loss of mcm-4 causes **failure of DNA replication with continued mitotic chromosome segregation**, **genome fragmentation**, and defective checkpoint responses. Postembryonic somatic lineages are strongly affected, while gonad/germline can continue divisions longer, likely due to maternal product and stronger checkpoint buffering. | Worm primary | Korzelius et al., 2011, https://doi.org/10.1016/j.ydbio.2010.12.009 | (pqac-00000015, pqac-00000018, pqac-00000020, pqac-00000021) |
| Tissue-specific requirements | Although mcm-4 has a general replication role, worm experiments show an **epidermis-specific requirement for organismal growth and viability**. **Pdpy-7::MCM-4::mCherry** rescues larval growth and viability, while intestine-specific expression rescues intestinal nuclear divisions/endoreduplication but not whole-animal viability. This indicates strong tissue-specific sensitivity despite conserved core function. | Worm primary | Korzelius et al., 2011, https://doi.org/10.1016/j.ydbio.2010.12.009 | (pqac-00000016, pqac-00000017, pqac-00000023) |
| Replication-independent / beyond-replication roles | Recent C. elegans work on **CMG**, though centered on **PSF-2/GINS2** rather than mcm-4 directly, shows that the replicative helicase can influence **asymmetric cell-fate divergence** and **egl-1 transcription** through a proposed **histone-chaperone / chromatin inheritance** mechanism that is separable from bulk DNA unwinding. This is relevant for interpreting potential noncanonical roles of MCM4-containing CMG in worms. | Worm primary (complex-level inference, not mcm-4-specific) | Memar et al., 2024, https://doi.org/10.1038/s41467-024-53715-2; Rankin & Rankin, 2024, https://doi.org/10.3390/biology13040258 | (pqac-00000036, pqac-00000037, pqac-00000038, pqac-00000039, pqac-00000040) |
| Recent structural/mechanistic developments (2023-2024) | 2023-2024 studies sharpen the mechanism of MCM activation: loaded double hexamers are converted into active CMG by **DDK/CDK-dependent phosphorylation**, recruitment of **Cdc45/GINS/Polε**, and **Mcm10-triggered helicase splitting/origin melting**. Cryo-EM visualized local origin unwinding, including **~0.7 turns untwisted** and **≥3 bp broken** in early activation intermediates. | Cross-species primary structural + review | Henrikus et al., 2024, https://doi.org/10.1038/s41594-024-01280-z; You & Masai, 2024, https://doi.org/10.3390/biology13080629; Weissmann et al., 2024, https://doi.org/10.1038/s41586-024-08263-6 | (pqac-00000008, pqac-00000009, pqac-00000013, pqac-00000035) |
| Applications / real-world implementations | In worms, **MCM-4 promoter/reporters** are used as practical **cell-cycle entry and proliferation markers**; live **MCM-4::mCherry** supports lineage-level imaging of licensing dynamics. More broadly, the CMG/MCM ATPase has become a tractable intervention point: 2024 work identified **ATP-competitive CMG/MCM inhibitors** (e.g., **clorobiocin**, **coumermycin-A1**) that disrupt helicase assembly and fork function, illustrating translational relevance of the MCM4-containing complex. | Worm tool + cross-species therapeutic application | van Rijnberk et al., 2017, https://doi.org/10.1371/journal.pone.0171600; Ruijtenberg et al., 2011, https://doi.org/10.5772/19397; Xiang et al., 2024, https://doi.org/10.1158/1535-7163.mct-23-0904 | (pqac-00000033, pqac-00000034) |
| Key quantitative / statistical data points | **MCM-4 protein** predicted at **823 aa** in C. elegans. In structural activation intermediates, origin DNA is **untwisted by ~0.7 turns** with **at least 3 bp broken**. In the 2024 CMG fate-divergence study, the C. elegans soma produces **1090 somatic cells**, **131 die**, and apoptosis occurs **~20–30 min** after terminal division; in psf-2(t3443ts), **67%** of MSpaapp deaths were blocked and AMso fate defects reached **82% (167/204)** among divisions scored. | Mixed: worm primary + cross-species structural + worm primary beyond-replication | Korzelius et al., 2011, https://doi.org/10.1016/j.ydbio.2010.12.009; Henrikus et al., 2024, https://doi.org/10.1038/s41594-024-01280-z; Memar et al., 2024, https://doi.org/10.1038/s41467-024-53715-2 | (pqac-00000000, pqac-00000035, pqac-00000036, pqac-00000039, pqac-00000040) |


*Table: This table condenses the most relevant identity, function, localization, phenotype, and recent mechanistic findings for C. elegans mcm-4/lin-6. It separates direct worm evidence from cross-species mechanistic inference and provides citation IDs for efficient reuse in the final report.*