Protein: DNA-directed primase/polymerase protein (EC 2.7.7.102) (EC 2.7.7.7) (Q6P1E7)
Organism: Mus musculus (Mouse)
Function: DNA primase and DNA polymerase required to tolerate replication-stalling lesions by bypassing them. Required to facilitate mitochondrial and nuclear replication fork progression by initiating de novo DNA synthesis using dNTPs and acting as an error-prone DNA polymerase able to bypass certain DNA lesions (By similarity). Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA (By similarity). Provides different translesion synthesis alternatives when DNA replication is stalled: able to synthesize DNA primers downstream of lesions, such as ultraviolet (UV) lesions, R-loops and G-quadruplexes, to allow DNA replication to continue (By similarity). Can also realign primers ahead of 'unreadable lesions' such as abasic sites and 6-4 photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping the lesion (By similarity). Also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase (By similarity). Also required for reinitiating stalled forks after UV damage during nuclear DNA replication (By similarity). Required for mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating synthesis after UV damage or in the presence of chain-terminating nucleotides. Prevents APOBEC family-mediated DNA mutagenesis by repriming downstream of abasic site to prohibit error-prone translesion synthesis. Has non-overlapping function with POLH (By similarity). In addition to its role in DNA damage response, also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells (By similarity).
Subcellular location: Nucleus {ECO:0000250|UniProtKB:Q96LW4}. Mitochondrion matrix {ECO:0000250|UniProtKB:Q96LW4}. Chromosome {ECO:0000250|UniProtKB:Q96LW4}. Note=Present in the nucleus, but a larger fraction is localized inside mitochondria. Associates with nuclear chromatin during the G1 and S phases of unperturbed cell cycles. Recruited to stalled replication forks following interaction with RPA1. {ECO:0000250|UniProtKB:Q96LW4}.
Interaction partners:
- SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A-like protein 1
- Replication protein A 70 kDa DNA-binding subunit
- Claspin
- TIMELESS-interacting protein
- Protein timeless homolog
- Replication protein A 14 kDa subunit
- E3 ubiquitin-protein ligase RFWD3
- DNA annealing helicase and endonuclease ZRANB3
- Replication protein A 32 kDa subunit
- Bifunctional 3'-5' exonuclease/ATP-dependent helicase WRN
Sequence:
MLRKWEARVKQIEERASHYERKPLSSVYRPRLAKPEEPSSIWKLFHRQNQAFNFVKSCKESVHVFALECKRGNGQRIYLVTSYAQLWFYYKTRKTLLHCYEVIPENAVCKLYFDLEFNKLANPGADGKMMVALLIQHVCKALEEFYNVQCSAEDVFNLDSSTEEKFSRHLIFQLHNVAFKDNRHAGNFVRKILQPALHLIAEDDEAKVPEAVGQDASGFSVTPLKQEISEAREKVGLPKQCDPDLSFLVVKNHMGEKCLFVDLGVYTKNRNFRLYQSSKIGKCVSLEVAEDNRFIPKQSKDISEENQYFLSSLVSNVRFSDTLRVLTCHPSQTKRKRAECFNSTGTSVESIEGFQGSPYPEVDQFVLSLVNKHDIKGGIRRWNYFFPEELLVYDICKYRWCENIGRAHKSNNIMILVDLKNEVWYQKCHDPVCKAQNFKSTCSPLPTEVSLLFLLKDEDFTSGETDDTSTSLTKDSQTPPSCNLSAGGLSAAAWDDEDDALFLEATEDAEFADAADKSLGSMDDIPDELIIEALQNS