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). Can act both with Mn(2+) and Mg(2+) as cofactor in vitro, but Mn(2+) is the preferred cofactor in vivo (PubMed:25255211, PubMed:25746449, PubMed:27989484, PubMed:30889508, PubMed:30633872). The polymerase activity incorporates correct dNTPs with much higher efficiency with Mn(2+) than with Mg(2+) (PubMed:25255211, PubMed:30889508). The fidelity is slightly more accurate when Mg(2+) is the cofactor compared to Mn(2+) (PubMed:25255211, PubMed:30889508). In the presence of Mn(2+), a conformational transition step from non-productive to productive PRIMPOL:DNA complexes limits the enzymatic turnover, whereas in the presence of Mg(2+), the chemical step becomes rate limiting (PubMed:30633872). kcat is 0.05 sec(-1) for dTTP (in presence of 2 mM of Mn(2+). kcat is 0.02 sec(-1) for dTTP (in presence of 50 uM of Mn(2+). kcat is 0.01 sec(-1) for dTTP (in presence of 2 mM of Mg(2+). 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). 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). The zinc knuckle motif binds zinc and is required for the DNA primase activity (PubMed:24682820, PubMed:29608762). It facilitates the binding and selection of the 5'-nucleotide of the newly synthesized primer and the recognition of preferred initiation sites (PubMed:29608762). The RPA1-binding motifs (RBM) mediate interaction with RPA1 and are essential for recruitment to chromatin (PubMed:28534480). The interaction is primarily mediated by RPA1-binding motif 1, which binds to the basic cleft of RPA1, with motif 2 plays a supporting role in RPA1-binding (PubMed:28534480). The presence of an Asp-Aaa-Glu (DxE) motif in the metal-binding active site favors the use of Mn(2+) ions to achieve optimal incoming nucleotide stabilization, especially required during primer synthesis (PubMed:30889508). Glu-116 is required to stabilize the incoming nucleotide at the 3'-site (PubMed:30889508). The disease is caused by variants affecting the gene represented in this entry. Belongs to the eukaryotic-type primase small subunit family. According to a report, the association between the variant Asp-89 and high myopia MYP22 is unclear as this variant is found in control populations (PubMed:25680975). The paper also questions the relevance of functional study on this variant (PubMed:25680975). Authors of the functional characterization study replied that their analysis clearly shows that Asp-89 variant affects the DNA polymerase and primase activities, regardless of its association with high myopia MYP22 (PubMed:25680976). Additional studies are therefore required to confirm the link between this variant and high myopia MYP22.