| Description |
DNA primase and DNA polymerase required to tolerate replication-stalling lesions by bypassing them (PMID:24126761, PMID:24207056, PMID:24240614, PMID:24267451, PMID:25255211, PMID:24682820, PMID:25262353, PMID:25746449, PMID:25550423, PMID:27989484, PMID:29608762, PMID:30889508, PMID:28534480). 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 (PMID:24126761, PMID:24207056, PMID:24240614, PMID:24267451, PMID:25255211, PMID:24682820, PMID:25262353, PMID:25746449, PMID:25550423, PMID:27989484, PMID:29608762, PMID:30889508, PMID:30633872, PMID:28534480). Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA (PMID:24126761, PMID:24207056, PMID:24240614, PMID:24267451, PMID:25746449). 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 (PMID:24240614, PMID:26626482, PMID:28534480, PMID:30478192). Can also realign primers ahead of 'unreadable lesions' such as abasic sites and 6-4 photoproduct (6-4 pyrimidine-pyrimidinone), thereby skipping the lesion (PMID:25746449). Also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase (PMID:24207056, PMID:25255211, PMID:25746449). Also required for reinitiating stalled forks after UV damage during nuclear DNA replication (PMID:24240614). Required for mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating synthesis after UV damage or in the presence of chain-terminating nucleotides (PMID:24207056). Prevents APOBEC family-mediated DNA mutagenesis by repriming downstream of abasic site to prohibit error-prone translesion synthesis . Has non-overlapping function with POLH (PMID:24240614). In addition to its role in DNA damage response, also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells (PMID:30715459). 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 (PMID:31676232). Repriming rescues fork degradation while leading to accumulation of internal ssDNA gaps behind the forks (PMID:31676232). ATR regulates adaptive response to cisplatin (PMID:31676232). |
