| Aspect | Evidence summary | Key citations |
|---|---|---|
| Identity | The target is mouse **Dnmt1** (UniProt **P13864**), the canonical maintenance DNA methyltransferase in vertebrates. Evidence in the retrieved literature consistently describes DNMT1/Dnmt1 as the enzyme that preserves CpG methylation patterns during DNA replication and specifically recognizes hemimethylated DNA. | (pqac-00000002, pqac-00000003, pqac-00000007) |
| Enzymatic reaction/cofactor | DNMT1 is a **DNA (cytosine-5)-methyltransferase** that transfers a methyl group from **S-adenosylmethionine (SAM)** to the 5-position of cytosine in CpG dinucleotides, producing 5-methylcytosine. This matches the UniProt annotation EC 2.1.1.37 and class I-like SAM-dependent C5 methyltransferase family assignment. | (pqac-00000002, pqac-00000003, pqac-00000006) |
| Substrate specificity | DNMT1 shows a strong **preference for hemimethylated CpG DNA** over unmethylated DNA, fitting its role in copying methylation after replication rather than establishing new methylation broadly de novo. The CXXC-linked autoinhibitory mechanism further helps prevent inappropriate methylation of unmethylated CpGs. | (pqac-00000000, pqac-00000001, pqac-00000004) |
| Key domains | Evidence supports the expected DNMT1 architecture: **PBD/PCNA-binding region**, **RFTS** autoinhibitory/replication-targeting module, **CXXC** domain that binds unmethylated CpG, **BAH1/BAH2** domains, and the **C-terminal catalytic C5 methyltransferase domain**. These domains align with the UniProt family/domain description for P13864. | (pqac-00000001, pqac-00000002, pqac-00000007) |
| Localization | DNMT1 is primarily **nuclear** and **colocalizes with replication foci during S phase**; outside S phase it is more diffusely nuclear but can remain associated with methylated heterochromatin. This localization is consistent with replication-coupled maintenance methylation. | (pqac-00000000, pqac-00000002, pqac-00000005) |
| Recruitment/activation mechanism | Current evidence supports a model in which **UHRF1** recognizes hemimethylated CpGs and ubiquitylates **histone H3 (K18/K23)** and **PAF15**, whose ubiquitin marks bind the **DNMT1 RFTS** domain and relieve autoinhibition. PCNA interaction contributes to replication-site targeting, but the DNMT1-PCNA interaction alone appears to make only a modest contribution relative to UHRF1-dependent mechanisms. | (pqac-00000001, pqac-00000002, pqac-00000005, pqac-00000016) |
| Key interactors | The strongest supported interactors/pathway components are **UHRF1**, **PCNA**, **PAF15**, and chromatin-associated ubiquitin/H3K9me3-linked signals; additional reported partners include **HDAC1** and **G9a**. Together these place DNMT1 in the maintenance methylation pathway that couples DNA replication to chromatin-state inheritance. | (pqac-00000000, pqac-00000003, pqac-00000005, pqac-00000006) |
| 2023-2024 mouse phenotypes/data | In mice, early cranial neural crest **Dnmt1** loss caused highly penetrant cleft palate (**24/24** or **27/28** depending on cross) with reduced maxillary mesenchyme 5-mC and reduced EdU labeling; pharmacologic DNMT inhibition caused stage-dependent cleft palate with peak incidence **30/51 (59%)** at GD9.75, while later exposure did not. A 2024 SHH medulloblastoma study identified **Dnmt1** as a druggable dependency required for murine cerebellar development and tumor growth in vivo, with DNMT1 inhibition suppressing tumor growth and prolonging survival in mouse models. | (pqac-00000008, pqac-00000009, pqac-00000011, pqac-00000012) |
| 2024 structural update | A 2024 JBC study identified a previously unreported **conserved N-terminal α-helical folded domain** in human DNMT1, expanding the structural map of the N-terminus beyond the classic annotated modules. Although not mouse-specific, this update is directly relevant because DNMT1 is highly conserved and informs functional annotation of mouse Dnmt1. | (pqac-00000007) |


*Table: This table condenses the key functional annotation points for mouse Dnmt1 (UniProt P13864), including catalytic activity, domains, localization, regulation, and recent mouse phenotype evidence. It is useful as a citation-linked overview for drafting the full research report.*