Low-fidelity DNA polymerase with a helicase activity that promotes microhomology-mediated end-joining (MMEJ), an alternative non-homologous end-joining (NHEJ) machinery required to repair double-strand breaks in DNA during mitosis (PubMed:14576298, PubMed:18503084, PubMed:24648516, PubMed:25642963, PubMed:25643323, PubMed:25775267, PubMed:26636256, PubMed:27311885, PubMed:27591252, PubMed:30655289, PubMed:31562312, PubMed:32873648, PubMed:34140467, PubMed:34179826, PubMed:36455556, PubMed:37440612, PubMed:37674080). MMEJ is an error-prone repair pathway that produces deletions of sequences from the strand being repaired and promotes genomic rearrangements, such as telomere fusions, some of them leading to cellular transformation (PubMed:25642963, PubMed:25643323, PubMed:25775267, PubMed:27311885, PubMed:27591252, PubMed:31562312, PubMed:32873648). MMEJ is required during mitosis to repair persistent double-strand breaks that originate in S-phase (PubMed:37440612, PubMed:37674080). Although error-prone, MMEJ protects against chromosomal instability and tumorigenesis (By similarity). The polymerase acts by binding directly the 2 ends of resected double-strand breaks, allowing microhomologous sequences in the overhangs to form base pairs (PubMed:25643323, PubMed:25775267, PubMed:27311885, PubMed:27591252). It then extends each strand from the base-paired region using the opposing overhang as a template (PubMed:25643323, PubMed:25775267, PubMed:27311885, PubMed:27591252). Requires partially resected DNA containing 2 to 6 base pairs of microhomology to perform MMEJ (PubMed:25643323, PubMed:25775267, PubMed:27311885, PubMed:27591252). The polymerase lacks proofreading activity and is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates (PubMed:18503084, PubMed:21050863, PubMed:22135286). When the ends of a break do not contain terminal microhomology must identify embedded complementary sequences through a scanning step (PubMed:32234782). Also shows endonuclease activity, which is required to trim the 3′ ends before synthesis can occur, thereby preventing non-paired tails (PubMed:33577776). Also acts as a DNA helicase, promoting dissociation of the replication protein A complex (RPA/RP-A), composed of RPA1, RPA2 and RPA3, from resected double-strand breaks to allow their annealing and subsequent joining by MMEJ (PubMed:36455556). Removal of RPA/RP-A complex proteins prevents RAD51 accumulation at resected ends, thereby inhibiting homology-recombination repair (HR) pathway (PubMed:25642963, PubMed:28695890). Also shows RNA-directed DNA polymerase activity to mediate DNA repair in vitro; however this activity needs additional evidence in vivo (PubMed:34117057). May also have lyase activity (PubMed:19188258). Involved in somatic hypermutation of immunoglobulin genes, a process that requires the activity of DNA polymerases to ultimately introduce mutations at both A/T and C/G base pairs (By similarity). POLQ-mediated end joining activity is involved in random integration of exogenous DNA hampers (PubMed:28695890).
