PRIMPOL
Description
The PRIMPOL (primase and DNA directed polymerase) is a protein-coding gene located on chromosome 4.
PRIMPOL is a DNA-directed primase/polymerase protein (hPrimpol1) also known as Coiled-coil domain-containing protein 111. DNA primase and DNA polymerase required to tolerate replication-stalling lesions by bypassing them (PubMed:24126761, PubMed:24207056, PubMed:24240614, PubMed:24267451, PubMed:24682820, PubMed:25255211, PubMed:25262353, PubMed:25550423, PubMed:25746449, PubMed:27989484, PubMed:28534480, PubMed:29608762, PubMed:30889508, PubMed:31676232). 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 (PubMed:24126761, PubMed:24207056, PubMed:24240614, PubMed:24267451, PubMed:25255211, PubMed:24682820, PubMed:25262353, PubMed:25746449, PubMed:25550423, PubMed:27989484, PubMed:29608762, PubMed:30889508, PubMed:30633872, PubMed:28534480). Shows a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA (PubMed:24126761, PubMed:24207056, PubMed:24240614, PubMed:24267451, PubMed: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 (PubMed:24240614, PubMed:26626482, PubMed:28534480, PubMed: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. Repriming avoids fork degradation while leading to accumulation of internal ssDNA gaps behind the forks (PubMed:24240614, PubMed:25746449, PubMed:31676232). Also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase (PubMed:24207056, PubMed:25255211, PubMed:25746449). Also required for reinitiating stalled forks after UV damage during nuclear DNA replication (PubMed:24240614). Required for mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating synthesis after UV damage or in the presence of chain-terminating nucleotides (PubMed:24207056). 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 (PubMed:24240614). In addition to its role in DNA damage response, also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells (PubMed:30715459). Interacts with RPA1; leading to recruitment to chromatin and stimulate DNA primase activity (PubMed:24126761, PubMed:25550423, PubMed:28396594, PubMed:28534480). Interacts with SSBP1 (PubMed:25550423). Interacts with POLDIP2; leading to enhance DNA polymerase activity (PubMed:26984527).
PRIMPOL is a DNA primase and polymerase that plays a critical role in tolerating DNA replication-stalling lesions by bypassing them. It facilitates 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. PRIMPOL exhibits a high capacity to tolerate DNA damage lesions such as 8oxoG and abasic sites in DNA. It provides different translesion synthesis alternatives when DNA replication is stalled, including synthesizing DNA primers downstream of lesions like ultraviolet (UV) lesions, R-loops and G-quadruplexes, and realigning primers ahead of 'unreadable lesions' such as abasic sites and 6-4 photoproduct, thereby skipping the lesion. PRIMPOL is also able to incorporate nucleotides opposite DNA lesions such as 8oxoG, like a regular translesion synthesis DNA polymerase. It is required for reinitiating stalled forks after UV damage during nuclear DNA replication and for mitochondrial DNA (mtDNA) synthesis and replication, by reinitiating synthesis after UV damage or in the presence of chain-terminating nucleotides. PRIMPOL prevents APOBEC family-mediated DNA mutagenesis by repriming downstream of abasic sites to prohibit error-prone translesion synthesis. It has non-overlapping function with POLH. In addition to its role in DNA damage response, PRIMPOL is also required to maintain efficient nuclear and mitochondrial DNA replication in unperturbed cells.
PRIMPOL is also known as CCDC111, MYP22, Primpol1.
