UniProt functional annotation for O75417



	UniProt functional annotation for O75417

UniProt code: O75417.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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 (PubMed:25642963, PubMed:25643323). 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). POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends (PubMed:25642963). 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 (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 (PubMed:25643323). The polymerase activity is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates (PubMed:18503084, PubMed:21050863, PubMed:22135286). 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 (PubMed:14576298, PubMed:18503084, PubMed:19188258, PubMed:24648516). 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). {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}.

Catalytic activity: Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:11130, Rhea:RHEA-COMP:11131, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:83828; EC=2.7.7.7; Evidence={ECO:0000269|PubMed:14576298, ECO:0000269|PubMed:22135286};

Biophysicochemical properties: Kinetic parameters: KM=1.095 uM for dATP:T {ECO:0000269|PubMed:22135286}; KM=0.622 uM for dATP: abasic site {ECO:0000269|PubMed:22135286}; KM=3.08 uM for dGTP: no template {ECO:0000269|PubMed:22135286};

Subunit: Homomultimer; forms dimers and multimers (PubMed:25643323). Interacts with RAD51 (PubMed:25642963). Interacts with ORC2 and ORC4 (PubMed:24989122). {ECO:0000269|PubMed:24989122, ECO:0000269|PubMed:25642963, ECO:0000269|PubMed:25643323}.

Subcellular location: Nucleus {ECO:0000250|UniProtKB:O18475}. Chromosome {ECO:0000269|PubMed:25642963}. Note=Enriched in chromatin in response to ultaviolet (UV) light (PubMed:25642963). Binds to chromatin during early G1 (PubMed:24989122). {ECO:0000269|PubMed:24989122, ECO:0000269|PubMed:25642963}.

Tissue specificity: Highly expressed in testis. {ECO:0000269|PubMed:14576298}.

Domain: The loop 2 region is involved in the binding of the 2 ends of resected double-strand breaks and homomultimerization. {ECO:0000269|PubMed:25643323}.

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.

Similarity: Belongs to the DNA polymerase type-A family. {ECO:0000305}.

Sequence caution: Sequence=AAD05272.1; Type=Frameshift; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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 (PubMed:25642963, PubMed:25643323). 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). POLQ acts as an inhibitor of homology-recombination repair (HR) pathway by limiting RAD51 accumulation at resected ends (PubMed:25642963). 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 (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 (PubMed:25643323). The polymerase activity is highly promiscuous: unlike most polymerases, promotes extension of ssDNA and partial ssDNA (pssDNA) substrates (PubMed:18503084, PubMed:21050863, PubMed:22135286). 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 (PubMed:14576298, PubMed:18503084, PubMed:19188258, PubMed:24648516). 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). {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}.


Catalytic activity:		Reaction=a 2'-deoxyribonucleoside 5'-triphosphate + DNA(n) = diphosphate + DNA(n+1); Xref=Rhea:RHEA:22508, Rhea:RHEA-COMP:11130, Rhea:RHEA-COMP:11131, ChEBI:CHEBI:33019, ChEBI:CHEBI:61560, ChEBI:CHEBI:83828; EC=2.7.7.7; Evidence={ECO:0000269\|PubMed:14576298, ECO:0000269\|PubMed:22135286};
Biophysicochemical properties:		Kinetic parameters: KM=1.095 uM for dATP:T {ECO:0000269\|PubMed:22135286}; KM=0.622 uM for dATP: abasic site {ECO:0000269\|PubMed:22135286}; KM=3.08 uM for dGTP: no template {ECO:0000269\|PubMed:22135286};
Subunit:		Homomultimer; forms dimers and multimers (PubMed:25643323). Interacts with RAD51 (PubMed:25642963). Interacts with ORC2 and ORC4 (PubMed:24989122). {ECO:0000269\|PubMed:24989122, ECO:0000269\|PubMed:25642963, ECO:0000269\|PubMed:25643323}.
Subcellular location:		Nucleus {ECO:0000250\|UniProtKB:O18475}. Chromosome {ECO:0000269\|PubMed:25642963}. Note=Enriched in chromatin in response to ultaviolet (UV) light (PubMed:25642963). Binds to chromatin during early G1 (PubMed:24989122). {ECO:0000269\|PubMed:24989122, ECO:0000269\|PubMed:25642963}.
Tissue specificity:		Highly expressed in testis. {ECO:0000269\|PubMed:14576298}.
Domain:		The loop 2 region is involved in the binding of the 2 ends of resected double-strand breaks and homomultimerization. {ECO:0000269\|PubMed:25643323}.
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.
Similarity:		Belongs to the DNA polymerase type-A family. {ECO:0000305}.
Sequence caution:		Sequence=AAD05272.1; Type=Frameshift; Evidence={ECO:0000305};