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FUNCTION DNA polymerase specifically involved in the DNA repair by translesion synthesis (TLS) (PubMed:10385124, PubMed:11743006, PubMed:16357261, PubMed:20388628, PubMed:24449906, PubMed:24553286, PubMed:38212351). Due to low processivity on both damaged and normal DNA, cooperates with the heterotetrameric (REV3L, REV7, POLD2 and POLD3) POLZ complex for complete bypass of DNA lesions. Inserts one or 2 nucleotide(s) opposite the lesion, the primer is further extended by the tetrameric POLZ complex. In the case of 1,2-intrastrand d(GpG)-cisplatin cross-link, inserts dCTP opposite the 3' guanine (PubMed:24449906). Particularly important for the repair of UV-induced pyrimidine dimers (PubMed:10385124, PubMed:11743006). Although inserts the correct base, may cause base transitions and transversions depending upon the context. May play a role in hypermutation at immunoglobulin genes (PubMed:11376341, PubMed:14734526). Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have any lyase activity, preventing the release of the 5'-deoxyribose phosphate (5'-dRP) residue. This covalent trapping of the enzyme by the 5'-dRP residue inhibits its DNA synthetic activity during base excision repair, thereby avoiding high incidence of mutagenesis (PubMed:14630940). Targets POLI to replication foci (PubMed:12606586).CATALYTIC ACTIVITY DNA(n) + a 2'-deoxyribonucleoside 5'-triphosphate = DNA(n+1) + diphosphateCOFACTOR Binds 2 Mg(2+) (PubMed:27284197). Prefers Mg(2+), but can also use Mn(2+) (PubMed:27284197). In vitro, can also utilize other divalent cations such as Ca(2+) (PubMed:27284197).ACTIVITY REGULATION The enzyme in complex with the DNA substrate binds a third divalent metal cation (PubMed:27284197). The binding of this third divalent cation, which is coordinated by water molecules and two oxygen atoms from DNA and dNTP, is essential for catalyzing the DNA synthesis (PubMed:27284197).BIOPHYSICOCHEMICAL PROPERTIES Interacts with REV1 (via C-terminal domain) (PubMed:22691049). Interacts with monoubiquitinated PCNA, but not unmodified PCNA (PubMed:15149598). Interacts with POLI; this interaction targets POLI to the replication machinery (PubMed:12606586). Interacts with PALB2 and BRCA2; the interactions are direct and are required to sustain the recruitment of POLH at blocked replication forks and to stimulate POLH-dependent DNA synthesis on D loop substrates (PubMed:24485656). Interacts (via C-terminus) with TRAIP (PubMed:24553286). Interacts with ubiquitin (PubMed:16357261). Interacts with POLDIP2 (PubMed:20554254).SUBCELLULAR LOCATION Binding to ubiquitinated PCNA mediates colocalization to replication foci during DNA replication and persists at sites of stalled replication forks following UV irradiation (PubMed:12606586, PubMed:16357261, PubMed:24553286). After UV irradiation, recruited to DNA damage sites within 1 hour, to a maximum of about 80%; this recruitment may not be not restricted to cells active in DNA replication (PubMed:22801543). Colocalizes with TRAIP to nuclear foci (PubMed:24553286).ALTERNATIVE PRODUCTS The catalytic core consists of fingers, palm and thumb subdomains, but the fingers and thumb subdomains are much smaller than in high-fidelity polymerases; residues from five sequence motifs of the Y-family cluster around an active site cleft that can accommodate DNA and nucleotide substrates with relaxed geometric constraints, with consequently higher rates of misincorporation and low processivity.DOMAIN The UBZ3-type zinc finger domain and the PIP-box mediate the interaction with ubiquitinated PCNA and are both necessary for the enzymatic activity in translesion synthesis.PTM Monoubiquitinated by RCHY1/PIRH2 (PubMed:20159558, PubMed:21791603). Ubiquitination depends on integrity of the UBZ3-type zinc finger domain and is enhanced by TRAIP (PubMed:16357261, PubMed:24553286). Ubiquitination inhibits the ability of PolH to interact with PCNA and to bypass UV-induced lesions (PubMed:20159558, PubMed:21791603, PubMed:24553286).DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the DNA polymerase type-Y family.
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