PRIMPOL

PRIMPOL is a DNA primase-polymerase that belongs to a superfamily of archaeao-eukaryotic primases. Members of this family have primase activity, catalyzing the synthesis of short RNA primers that serve as starting points for DNA synthesis, as well as DNA polymerase activity. The encoded protein facilitates DNA damage tolerance by mediating uninterrupted fork progression after UV irradiation and reinitiating DNA synthesis.

Primase And DNA Directed Polymerase

DNA primase and DNA polymerase required to tolerate replication-stalling lesions by bypassing them (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: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 (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 (PubMed:25746449).
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).
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 (PubMed:31676232).
Repriming rescues fork degradation while leading to accumulation of internal ssDNA gaps behind the forks (PubMed:31676232).
ATR regulates adaptive response to cisplatin (PubMed:31676232).

Error-prone translesion synthesisManual Assertion Based On ExperimentIDA:UniProtKB
Mitochondrial DNA repairISS:UniProtKB
Mitochondrial DNA replicationManual Assertion Based On ExperimentIMP:UniProtKB
R-loop disassemblyManual Assertion Based On ExperimentIDA:UniProtKB
Replication fork processingManual Assertion Based On ExperimentIDA:UniProtKB
Response to UVManual Assertion Based On ExperimentIDA:UniProtKB
Translesion synthesisManual Assertion Based On ExperimentIMP:UniProtKB

Nucleus
Mitochondrion matrix
Chromosome
Present in the nucleus, but a larger fraction is localized inside mitochondria (PubMed:24207056).
Associates with nuclear chromatin during the G1 and S phases of unperturbed cell cycles (PubMed:24207056).
Recruited to stalled replication forks following interaction with RPA1 (PubMed:28534480).

Myopia 22, autosomal dominant (MYP22):
A refractive error of the eye, in which parallel rays from a distant object come to focus in front of the retina, vision being better for near objects than for far.