UniprotKB/SwissProt ID: Q8CGS6 (Q8CGS6)
Gene Name:
Polq
Organism: Mus musculus (Mouse)
Function: 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:21883722, PubMed:25275444, PubMed:25642960, PubMed:25642963, PubMed:29079701, PubMed:31537809). 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:25275444, PubMed:25642960, PubMed:25642963, PubMed:29079701, PubMed:31537809). MMEJ is required during mitosis to repair persistent double-strand breaks that originate in S-phase (By similarity). Although error-prone, MMEJ protects against chromosomal instability and tumorigenesis (PubMed:30773314). The polymerase acts by binding directly the 2 ends of resected double-strand breaks, allowing microhomologous sequences in the overhangs to form base pairs (By similarity). It then extends each strand from the base-paired region using the opposing overhang as a template (By similarity). Requires partially resected DNA containing 2 to 6 base pairs of microhomology to perform MMEJ (By similarity). The polymerase lacks proofreading activity and is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates (By similarity). When the ends of a break do not contain terminal microhomology must identify embedded complementary sequences through a scanning step (By similarity). 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:29058711). Removal of RPA/RP-A complex proteins prevents RAD51 accumulation at resected ends, thereby inhibiting homology-recombination repair (HR) pathway (PubMed:25642960, PubMed:25642963, PubMed:29058711). Also shows RNA-directed DNA polymerase activity to mediate DNA repair in vitro; however this activity needs additional evidence in vivo (By similarity). May also have lyase activity (By similarity). 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 (PubMed:16172387, PubMed:16222339, PubMed:16890500, PubMed:17449470). However, POLQ does not play a major role in somatic hypermutation (PubMed:18485835). POLQ-mediated end joining activity is involved in random integration of exogenous DNA hampers (PubMed:28687761)
Other Modifications: View all modification sites in dbPTM
Protein Subcellular Localization: Nucleus. Chromosome
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