POLQ
entrez
10721
canonical
uniprot
O75417
canonical
ensembl
ENSG00000051341
resolver
ensp
ENSP00000264233
resolver
genesymbol
POLQ
resolver
genesymbol_syn
POLH
resolver
hgnc
HGNC:9186
resolver
uniprot
O95160
resolver
uniprot
Q59EE4
resolver
uniprot
Q6VMB5
resolver
uniprot_entry
DPOLQ_HUMAN
resolver
uniprot_entry
Q59EE4_HUMAN
resolver
uniprot_sec
O95160
resolver
uniprot_sec
Q6VMB5
resolver
activity_regulation
ACTIVITY REGULATION: Specifically inhibited by the antibiotic novobiocin (PubMed:34179826). The polymerase activity is specifically inhibited by the small molecule ART558 (PubMed:34140467). Novobiocin and ART558 confer specific killing of BRCA1/2-deficient cells and synergize with the poly [ADP-ribose] polymerase (PARP) inhibitor olaparib (PubMed:34140467, PubMed:34179826). {ECO:0000269|PubMed:34140467, ECO:0000269|PubMed:34179826}.
uniprot
proteins
amino_acid_sequence
MNLLRRSGKRRRSESGSDSFSGSGGDSSASPQFLSGSVLSPPPGLGRCLKAAAAGECKPTVPDYERDKLLLANWGLPKAVLEKYHSFGVKKMFEWQAECLLLGQVLEGKNLVYSAPTSAGKTLVAELLILKRVLEMRKKALFILPFVSVAKEKKYYLQSLFQEVGIKVDGYMGSTSPSRHFSSLDIAVCTIERANGLINRLIEENKMDLLGMVVVDELHMLGDSHRGYLLELLLTKICYITRKSASCQADLASSLSNAVQIVGMSATLPNLELVASWLNAELYHTDFRPVPLLESVKVGNSIYDSSMKLVREFEPMLQVKGDEDHVVSLCYETICDNHSVLLFCPSKKWCEKLADIIAREFYNLHHQAEGLVKPSECPPVILEQKELLEVMDQLRRLPSGLDSVLQKTVPWGVAFHHAGLTFEERDIIEGAFRQGLIRVLAATSTLSSGVNLPARRVIIRTPIFGGRPLDILTYKQMVGRAGRKGVDTVGESILICKNSEKSKGIALLQGSLKPVRSCLQRREGEEVTGSMIRAILEIIVGGVASTSQDMHTYAACTFLAASMKEGKQGIQRNQESVQLGAIEACVMWLLENEFIQSTEASDGTEGKVYHPTHLGSATLSSSLSPADTLDIFADLQRAMKGFVLENDLHILYLVTPMFEDWTTIDWYRFFCLWEKLPTSMKRVAELVGVEEGFLARCVKGKVVARTERQHRQMAIHKRFFTSLVLLDLISEVPLREINQKYGCNRGQIQSLQQSAAVYAGMITVFSNRLGWHNMELLLSQFQKRLTFGIQRELCDLVRVSLLNAQRARVLYASGFHTVADLARANIVEVEVILKNAVPFKSARKAVDEEEEAVEERRNMRTIWVTGRKGLTEREAAALIVEEARMILQQDLVEMGVQWNPCALLHSSTCSLTHSESEVKEHTFISQTKSSYKKLTSKNKSNTIFSDSYIKHSPNIVQDLNKSREHTSSFNCNFQNGNQEHQTCSIFRARKRASLDINKEKPGASQNEGKTSDKKVVQTFSQKTKKAPLNFNSEKMSRSFRSWKRRKHLKRSRDSSPLKDSGACRIHLQGQTLSNPSLCEDPFTLDEKKTEFRNSGPFAKNVSLSGKEKDNKTSFPLQIKQNCSWNITLTNDNFVEHIVTGSQSKNVTCQATSVVSEKGRGVAVEAEKINEVLIQNGSKNQNVYMKHHDIHPINQYLRKQSHEQTSTITKQKNIIERQMPCEAVSSYINRDSNVTINCERIKLNTEENKPSHFQALGDDISRTVIPSEVLPSAGAFSKSEGQHENFLNISRLQEKTGTYTTNKTKNNHVSDLGLVLCDFEDSFYLDTQSEKIIQQMATENAKLGAKDTNLAAGIMQKSLVQQNSMNSFQKECHIPFPAEQHPLGATKIDHLDLKTVGTMKQSSDSHGVDILTPESPIFHSPILLEENGLFLKKNEVSVTDSQLNSFLQGYQTQETVKPVILLIPQKRTPTGVEGECLPVPETSLNMSDSLLFDSFSDDYLVKEQLPDMQMKEPLPSEVTSNHFSDSLCLQEDLIKKSNVNENQDTHQQLTCSNDESIIFSEMDSVQMVEALDNVDIFPVQEKNHTVVSPRALELSDPVLDEHHQGDQDGGDQDERAEKSKLTGTRQNHSFIWSGASFDLSPGLQRILDKVSSPLENEKLKSMTINFSSLNRKNTELNEEQEVISNLETKQVQGISFSSNNEVKSKIEMLENNANHDETSSLLPRKESNIVDDNGLIPPTPIPTSASKLTFPGILETPVNPWKTNNVLQPGESYLFGSPSDIKNHDLSPGSRNGFKDNSPISDTSFSLQLSQDGLQLTPASSSSESLSIIDVASDQNLFQTFIKEWRCKKRFSISLACEKIRSLTSSKTATIGSRFKQASSPQEIPIRDDGFPIKGCDDTLVVGLAVCWGGRDAYYFSLQKEQKHSEISASLVPPSLDPSLTLKDRMWYLQSCLRKESDKECSVVIYDFIQSYKILLLSCGISLEQSYEDPKVACWLLDPDSQEPTLHSIVTSFLPHELPLLEGMETSQGIQSLGLNAGSEHSGRYRASVESILIFNSMNQLNSLLQKENLQDVFRKVEMPSQYCLALLELNGIGFSTAECESQKHIMQAKLDAIETQAYQLAGHSFSFTSSDDIAEVLFLELKLPPNREMKNQGSKKTLGSTRRGIDNGRKLRLGRQFSTSKDVLNKLKALHPLPGLILEWRRITNAITKVVFPLQREKCLNPFLGMERIYPVSQSHTATGRITFTEPNIQNVPRDFEIKMPTLVGESPPSQAVGKGLLPMGRGKYKKGFSVNPRCQAQMEERAADRGMPFSISMRHAFVPFPGGSILAADYSQLELRILAHLSHDRRLIQVLNTGADVFRSIAAEWKMIEPESVGDDLRQQAKQICYGIIYGMGAKSLGEQMGIKENDAACYIDSFKSRYTGINQFMTETVKNCKRDGFVQTILGRRRYLPGIKDNNPYRKAHAERQAINTIVQGSAADIVKIATVNIQKQLETFHSTFKSHGHREGMLQSDQTGLSRKRKLQGMFCPIRGGFFILQLHDELLYEVAEEDVVQVAQIVKNEMESAVKLSVKLKVKVKIGASWGELKDFDV
uniprot
proteins
disease_involvement
DISEASE: Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case. {ECO:0000269|PubMed:20624954, ECO:0000269|PubMed:20700469, ECO:0000269|PubMed:25409685}. Note=The gene represented in this entry may be involved in disease pathogenesis.
uniprot
proteins
ec_number
2.7.7.49
uniprot
proteins
ec_number
2.7.7.7
uniprot
proteins
ec_number
5.6.2.4
uniprot
proteins
function
FUNCTION: 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 (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). 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 (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). DNA helicase activity has been examined and has (PubMed:29444826) and has not (PubMed:14576298, PubMed:36455556) been demonstrated (PubMed:14576298, PubMed:29444826, PubMed:36455556). {ECO:0000250|UniProtKB:Q8CGS6, ECO:0000269|PubMed:14576298, ECO:0000269|PubMed:18503084, ECO:0000269|PubMed:19188258, ECO:0000269|PubMed:21050863, ECO:0000269|PubMed:22135286, ECO:0000269|PubMed:24648516, ECO:0000269|PubMed:25642963, ECO:0000269|PubMed:25643323, ECO:0000269|PubMed:25775267, ECO:0000269|PubMed:26636256, ECO:0000269|PubMed:27311885, ECO:0000269|PubMed:27591252, ECO:0000269|PubMed:28695890, ECO:0000269|PubMed:29444826, ECO:0000269|PubMed:30655289, ECO:0000269|PubMed:31562312, ECO:0000269|PubMed:32234782, ECO:0000269|PubMed:32873648, ECO:0000269|PubMed:34117057, ECO:0000269|PubMed:34140467, ECO:0000269|PubMed:34179826, ECO:0000269|PubMed:36455556, ECO:0000269|PubMed:37440612, ECO:0000269|PubMed:37674080}.
uniprot
proteins
mass_dalton
289619
uniprot
proteins
mutagenesis
MUTAGEN 121; /note="K->M: Loss of DNA helicase activity. Abolished ATPase activity."; /evidence="ECO:0000269|PubMed:29444826, ECO:0000269|PubMed:31562312"; MUTAGEN 1482..1493; /note="SLNMSDSLLFDS->ALNMADALLFDA: In 4S-P mutant; decreased phosphorylation by PLK1, leading to impaired interaction with TOPBP1 and recruitment to DNA damage sites."; /evidence="ECO:0000269|PubMed:37674080"; MUTAGEN 1977; /note="S->P: Decreased protein stability."; /evidence="ECO:0000305|PubMed:25775267"; MUTAGEN 2181; /note="K->A: Impaired ability to bypass abasic sites."; /evidence="ECO:0000269|PubMed:25775267"; MUTAGEN 2202; /note="R->A: Impaired ability to bypass abasic sites. In Pol-theta(RR) mutant; abolished polymerase activity; when associated with V-2254."; /evidence="ECO:0000269|PubMed:25775267, ECO:0000269|PubMed:27311885"; MUTAGEN 2254; /note="R->A,V: Impaired ability to bypass abasic sites."; /evidence="ECO:0000269|PubMed:25775267"; MUTAGEN 2254; /note="R->V: In Pol-theta(RR) mutant; abolished polymerase activity; when associated with A-2202."; /evidence="ECO:0000269|PubMed:27311885"; MUTAGEN 2540..2541; /note="DE->AA: Abolishes DNA polymerase activity."; /evidence="ECO:0000269|PubMed:19188258, ECO:0000269|PubMed:24648516
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by PLK1; promoting interaction with TOPBP1 and recruitment to DNA damage sites. {ECO:0000269|PubMed:37674080}.
uniprot
proteins
protein_family
DNA polymerase type-A family
uniprot
proteins
pubmed
10395804
uniprot
proteins
pubmed
14576298
uniprot
proteins
pubmed
16641997
uniprot
proteins
pubmed
18503084
uniprot
proteins
pubmed
19188258
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20624954
uniprot
proteins
pubmed
20700469
uniprot
proteins
pubmed
21050863
uniprot
proteins
pubmed
22135286
uniprot
proteins
pubmed
24648516
uniprot
proteins
pubmed
24989122
uniprot
proteins
pubmed
25409685
uniprot
proteins
pubmed
25642963
uniprot
proteins
pubmed
25643323
uniprot
proteins
pubmed
25775267
uniprot
proteins
pubmed
26636256
uniprot
proteins
pubmed
27311885
uniprot
proteins
pubmed
27591252
uniprot
proteins
pubmed
28695890
uniprot
proteins
pubmed
29444826
uniprot
proteins
pubmed
30655289
uniprot
proteins
pubmed
31562312
uniprot
proteins
pubmed
32234782
uniprot
proteins
pubmed
32273507
uniprot
proteins
pubmed
32873648
uniprot
proteins
pubmed
33577776
uniprot
proteins
pubmed
34117057
uniprot
proteins
pubmed
34140467
uniprot
proteins
pubmed
34179826
uniprot
proteins
pubmed
36455556
uniprot
proteins
pubmed
37440612
uniprot
proteins
pubmed
37674080
uniprot
proteins
pubmed
38640889
uniprot
proteins
pubmed
38640897
uniprot
proteins
sequence_length
2590
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:O18475}. Chromosome {ECO:0000269|PubMed:25642963, ECO:0000269|PubMed:34179826, ECO:0000269|PubMed:37440612, ECO:0000269|PubMed:37674080}. Note=Enriched in chromatin in response to ultaviolet (UV) light (PubMed:25642963, PubMed:34179826). Binds to chromatin during early G1 (PubMed:24989122). Recruited to DNA damage sites, such as double-stranded breaks (DSBs), following interaction with TOPBP1 and RHNO1 (PubMed:37440612, PubMed:37674080). {ECO:0000269|PubMed:24989122, ECO:0000269|PubMed:25642963, ECO:0000269|PubMed:34179826, ECO:0000269|PubMed:37440612, ECO:0000269|PubMed:37674080}.
uniprot
proteins