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 (      , ). Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA (  ). 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 ( , ). Can also realign primers ahead of 'unreadable lesions' such as abasic sites and 6-4 photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping the lesion . Also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase ( ). Also required for reinitiating stalled forks after UV damage during nuclear DNA replication . 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 (By similarity). Has non-overlapping function with POLH . In addition to its role in DNA damage response, also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells .
Involved in adaptive response to cisplatin, a chemotherapeutic that causes reversal of replication forks, in cancer cells: reinitiates DNA synthesis past DNA lesions in BRCA1-deficient cancer cells treated with cisplatin via its de novo priming activity . Repriming rescues fork degradation while leading to accumulation of internal ssDNA gaps behind the forks . ATR regulates adaptive response to cisplatin .
Subcellular locations: Nucleus, Mitochondrion matrix, Chromosome
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 .