Protein: DNA polymerase theta (Chromosome aberrations occurring spontaneously protein 1) (DNA polymerase eta) [Includes: Helicase POLQ (EC 3.6.4.12); DNA polymerase POLQ (EC 2.7.7.7) (RNA-directed DNA polymerase POLQ) (EC 2.7.7.49)] (Q8CGS6)
Organism: Mus musculus (Mouse)
Function: DNA polymerase that promotes microhomology-mediated end-joining (MMEJ), an alternative non-homologous end-joining (NHEJ) machinery triggered in response to double-strand breaks in DNA. 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. POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends. POLQ-mediated MMEJ may be required to promote the survival of cells with a compromised HR repair pathway, thereby preventing genomic havoc by resolving unrepaired lesions. 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 activity is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates. Also exhibits low-fidelity DNA synthesis, translesion synthesis and lyase activity, and it is implicated in interstrand-cross-link repair, base excision repair and DNA end-joining (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. However, POLQ does not play a major role in somatic hypermutation.
Subcellular location: Nucleus {ECO:0000250|UniProtKB:O18475}. Chromosome {ECO:0000250|UniProtKB:O75417}. Note=Enriched in chromatin in response to ultaviolet (UV) light. Binds to chromatin during early G1. Recruited to DNA damage sites, such as double-stranded breaks (DSBs), following interaction with TOPBP1 and RHNO1. {ECO:0000250|UniProtKB:O75417}.
Interaction partners:
- DNA endonuclease RBBP8
- Breast cancer type 2 susceptibility protein homolog
- Flap endonuclease 1
- Exonuclease 1
- Poly [ADP-ribose] polymerase 1
- DNA ligase 4
- Double-strand break repair protein MRE11
- Endonuclease 8-like 3
- Breast cancer type 1 susceptibility protein homolog
- Fanconi anemia group D2 protein homolog
Sequence:
MSLPRRSRKRRRSSSGSDTFSGDGDSFVSPQLRCGPVLSPPPGLGRGRRLTGTGTNKRRVSDDQIDQLLLANWGLPKAVLEKYHSFGVRKMFEWQAECLLLGHVLEGKNLVYSAPTSAGKTLVAELLILKRVLETRKKALFILPFVSVAKEKKCYLQSLFQEVGLKVDGYMGSTSPTGQFSSLDIAVCTIERANGLVNRLIEENKMDLLGMVVVDELHMLGDSHRGYLLELLLTKICYVTRKSASHQAESASTLSNAVQIVGMSATLPNLQLVASWLNAELYHTDFRPVPLLESIKIGNSIYDSSMKLVREFQPLLQVKGDEDHIVSLCYETIQDNHSVLIFCPSKKWCEKVADIIAREFYNLHHQPEGLVKSSEFPPVILDQKSLLEVMDQLKRSPSGLDSVLKNTVPWGVAFHHAGLTFEERDIIEGAFRQGFIRVLAATSTLSSGVNLPARRVIIRTPIFSGQPLDILTYKQMVGRAGRKGVDTMGESILVCKNSEKSKGIALLQGSLEPVHSCLQRQGEVTASMIRAILEIIVGGVASTSQDMQTYAACTFLAAAIQEGKQGMQRNQDDAQLGAIDACVTWLLENEFIQVAEPGDGTGGKVYHPTHLGSATLSSSLSPTDTLDIFADLQRAMKGFVLENDLHIVYLVTPVFEDWISIDWYRFFCLWEKLPTSMKRVAELVGVEEGFLARCVKGKVVARTERQHRQMAIHKRFFTSLVLLDLISEIPLKDINQKYGCNRGQIQSLQQSAAVYAGMITVFSNRLGWHNMELLLSQFQKRLTFGIQRELCDLIRVSLLNAQRARFLYASGFLTVADLARADSAEVEVALKNSLPFKSARKAVDEEEEAAEERRSMRTIWVTGKGLSAREAAALIVEEAKMILQQDLIEMGVRWDPKSPLSSSTHSRTSTSEVKEHTFKSQTKSSHKRLASMGRNSIRASGSNDKPSPDAERGIDDCSEHADSLCKFQGNFEPQTPSICTARKRTSLGINKEMLRKSLKEGKPSTKEVLQTFSSEKTRKTALSFSSEQVNNTLPSGRDRKYQKKSWGSSPVRDSGMHRGDLQGQTMCTSALCEDSQKSLEEQNAEFRSPGLFAKHLPSCAKEKCKKPSLPLQRQQACSRRSTESCAAVGHPAAGSSPAAARDRRGLAARETEKGNEALTENGGESQLQDTYPVSQYLEYHSEKHTNTCTRQKTLTEGQAGSSYVARDSNDAAPIKCERMKLNSKDRDSNPCRQALGSYTGRTEALQSTAKLGQAGGQCENLLNSSGVQGKTGAHATNRTEHSHASNPAFCDFGDSLDLDTQSEEIIEQMATENTMQGAKAVVIMEEGSAMQNKCHSTPGDQHVPGAANTDHVDSKKVESVKANTEKNINRGAPVSLIFHTQGENGACFKGNEHSVTDSQLNSFLQGFETQEIVKPIIPLAPQMRTPTGVEEESLPETSLNMSDSILFDSFGEDGFGQGQSPDIKANQPLLSEMTPNHFSNPPHPQEDPVMTPTVSEPQGTQQQGVCLSGESIIFSDIDSAQVIEALDNMAAFHVQENCNSVALKTLEPSDSAVLGNECPQGKLVRGDQNEGSPKPKLTETNQDNSFTWSGASFNLSPELQRILDKVSSPRENEKPKMIHVNLSSFEGNSKESHEREEINSDLGTVQRTSVFPSNEVKNRTEGLESKARHGGASSPLPRKESAAADDNGLIPPTPVPASASKVAFPEILGTSVKRQKASSALQPGESCLFGSPSDNQNQDLSQELRDSLKDYDGSVADTSFFLQSQDGLLLTQASCSSESLAIIDVASDQILFQTFVKEWQCQKRFSISLACEKMTSSMSSKTATIGGKLKQVSLPQEATVEDAGFPVRGCDGAVVVGLAVCWGAKDAYYLSLQKEQKQSEISPSLAPPPLDATLTVKERMECLQSCLQKKSDRERSVVTYDFIQTYKVLLLSCGISLEPSYEDPKVACWLLDPDSKEPTLHSIVTSFLPHELALLEGMETGPGIQSLGLNVNTEHSGRYRASVESVLIFNSMNQLNSLLQKENLHDIFCKVEMPSQYCLALLELNGIGFSTAECESQKHVMQAKLDAIETQAYQLAGHSFSFTSADDIAQVLFLELKLPPNGEMKTQGSKKTLGSTRRGNESGRRMRLGRQFSTSKDILNKLKGLHPLPGLILEWRRISNAITKVVFPLQREKHLNPLLRMERIYPVSQSHTATGRITFTEPNIQNVPRDFEIKMPTLVRESPPSQAPKGRFPMAIGQDKKVYGLHPGHRTQMEEKASDRGVPFSVSMRHAFVPFPGGLILAADYSQLELRILAHLSRDCRLIQVLNTGADVFRSIAAEWKMIEPDAVGDDLRQHAKQICYGIIYGMGAKSLGEQMGIKENDAASYIDSFKSRYKGINHFMRDTVKNCRKNGFVETILGRRRYLPGIKDDNPYHKAHAERQAINTTVQGSAADIVKIATVNIQKQLETFRSTFKSHGHRESMLQNDRTGLLPKRKLKGMFCPMRGGFFILQLHDELLYEVAEEDVVQVAQIVKNEMECAIKLSVKLKVKVKIGASWGELKDFDV