POLQ

Low-fidelity DNA polymerase with a putative 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. 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. MMEJ is required during mitosis to repair persistent double-strand breaks that originate in S-phase. 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. It then extends each strand from the base-paired region using the opposing overhang as a template. Requires partially resected DNA containing 2 to 6 base pairs of microhomology to perform MMEJ. The polymerase lacks proofreading activity and is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates. When the ends of a break do not contain terminal microhomology must identify embedded complementary sequences through a scanning step. Promotes 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. Removal of RPA/RP-A complex proteins prevents RAD51 accumulation at resected ends, thereby inhibiting homology-recombination repair (HR) pathway. Also shows RNA-directed DNA polymerase activity to mediate DNA repair in vitro; however this activity needs additional evidence in vivo. May also have lyase activity. 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. DNA helicase activity has been examined and has and has not been demonstrated..

Function from UniProtKB (O75417), read 2026-09-23. CC BY 4.0.