POLQ Antibody
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Product Specs
Target Background
Function
DNA polymerase theta (POLQ) is an enzyme that facilitates microhomology-mediated end-joining (MMEJ), an alternative pathway for repairing double-strand breaks in DNA. This pathway differs from the canonical non-homologous end-joining (NHEJ) mechanism. MMEJ is prone to errors, leading to deletions in the repaired strand and promoting genomic rearrangements such as telomere fusions. These rearrangements can contribute to cellular transformation.
Notably, POLQ acts as an inhibitor of homology-recombination repair (HR) by limiting RAD51 accumulation at resected DNA ends. This suggests that POLQ-mediated MMEJ plays a critical role in the survival of cells with impaired HR pathways, effectively preventing genomic instability by resolving unrepaired DNA lesions.
POLQ functions by directly binding to the two ends of resected double-strand breaks. This binding allows microhomologous sequences in the overhangs to align and base pair. The enzyme then extends each strand from the base-paired region, using the opposing overhang as a template. This process requires partially resected DNA with 2 to 6 base pairs of microhomology to execute MMEJ.
POLQ exhibits remarkable versatility in its polymerase activity. Unlike most DNA polymerases, it efficiently promotes extension of both single-stranded DNA (ssDNA) and partially single-stranded DNA (pssDNA) substrates. Additionally, it displays low-fidelity DNA synthesis, translesion synthesis, and lyase activity. These activities are implicated in various DNA repair processes, including interstrand-cross-link repair, base excision repair, and DNA end-joining. POLQ is also involved in somatic hypermutation of immunoglobulin genes, a process requiring DNA polymerase activity to introduce mutations at both A/T and C/G base pairs.
Notably, POLQ acts as an inhibitor of homology-recombination repair (HR) by limiting RAD51 accumulation at resected DNA ends. This suggests that POLQ-mediated MMEJ plays a critical role in the survival of cells with impaired HR pathways, effectively preventing genomic instability by resolving unrepaired DNA lesions.
POLQ functions by directly binding to the two ends of resected double-strand breaks. This binding allows microhomologous sequences in the overhangs to align and base pair. The enzyme then extends each strand from the base-paired region, using the opposing overhang as a template. This process requires partially resected DNA with 2 to 6 base pairs of microhomology to execute MMEJ.
POLQ exhibits remarkable versatility in its polymerase activity. Unlike most DNA polymerases, it efficiently promotes extension of both single-stranded DNA (ssDNA) and partially single-stranded DNA (pssDNA) substrates. Additionally, it displays low-fidelity DNA synthesis, translesion synthesis, and lyase activity. These activities are implicated in various DNA repair processes, including interstrand-cross-link repair, base excision repair, and DNA end-joining. POLQ is also involved in somatic hypermutation of immunoglobulin genes, a process requiring DNA polymerase activity to introduce mutations at both A/T and C/G base pairs.
Gene References Into Functions
- Cells lacking both Pol theta and Lig4 exhibit 100% gene-targeting efficiency due to the near absence of random integration events. PMID: 28695890
- Research suggests that translesion DNA synthesis, mediated by (1) POLI-dependent pathway (2) REV1- and POLN-dependent pathway, or (3) POLtheta-dependent pathway, occurs predominantly in an error-free manner in human cells. (POLI = DNA polymerase iota; REV1 = DNA repair protein-REV1; POLN = DNA polymerase nu; POLtheta = DNA polymerase theta) PMID: 29330301
- Findings indicate that bypass of Tg by Pol theta results in mutations opposite the lesion, as well as frameshift mutations. PMID: 29243925
- This article summarizes work on the expression and purification of the full-length protein and then focuses on the design, expression, and purification of an active C-terminal polymerase fragment. Strategies to obtain and improve crystals of a ternary POLQ complex (enzyme:DNA:nucleotide) are also presented, along with key structural elements. PMID: 28668117
- Our results indicate a synthetic lethal relationship between pol theta-mediated DNA repair and homologous recombination pathways. PMID: 27533083
- Data suggest that error-free DNA replication through 3-deaza-3-methyladenine adduct is mediated via three different pathways dependent upon POL-iota/POL-kappa, POL-theta, and POL-zeta. PMID: 28939775
- Fluorescence resonance energy transfer is used to monitor assembly of the human replicative polymerase holoenzyme. PMID: 23577232
- These results suggest that variants in the POLQ gene may be associated with the risk of Luminal breast cancer. PMID: 25417172
- A DNA repair variant in POLQ (c.-1060A > G) is associated with hereditary breast cancer patients. PMID: 25409685
- Polymerase theta utilizes a specialized thumb subdomain to establish unique upstream contacts to the primer DNA strand. PMID: 25775267
- Microhomology-mediated end-joining is dependent on Poltheta in human cells. PMID: 25643323
- Depletion of Poltheta has a synergistic effect on cell survival in the absence of BRCA genes, suggesting that inhibition of this mutagenic polymerase represents a viable therapeutic avenue for tumors carrying mutations in homology-directed repair genes. PMID: 25642960
- Results reveal a synthetic lethal relationship between the homologous-recombination pathway and Poltheta-mediated repair in epithelial ovarian cancers, identifying Poltheta as a novel druggable target for cancer therapy. PMID: 25642963
- A role for DNA polymerase theta in promoting replication through oxidative DNA lesion, thymine glycol, in human cells. PMID: 24648516
- POLQ possesses a DNA polymerase activity that appears to be template independent and allows efficient extension of single-stranded DNA as well as duplex DNA with either protruding or multiply mismatched 3'-OH termini. PMID: 22135286
- Overexpression in breast cancer confers an adverse prognosis and is associated with key cancer pathways. PMID: 20700469
- Data show that POLQ overexpression may be a promising genetic instability and prognostic marker for breast cancer. PMID: 20624954
- DNA polymerase theta purified from human cells is a high-fidelity enzyme. PMID: 12051913
- The isolation of the full-length human DNA POLQ gene and an initial characterization of its gene product, DNA polymerase theta. PMID: 14576298
- DNA Pol theta has a specialized function in lymphocytes and in tumor progression. PMID: 14735462
- POLQ exhibits high efficiency in by-passing DNA damage. PMID: 15496986
- Analysis of human DNA polymerase eta error-prone synthesis on DNA deoxyadenosine adducts. PMID: 16188888
- Results demonstrate that activation of a UV-induced DNA damage response pathway, involving phosphorylation of RPA p34 by DNA-PK, is enhanced in cells lacking poleta. PMID: 16520097
- Pol eta can play a significant role in determining the cellular sensitivity to therapeutic agents. PMID: 16603639
- DNA polymerase eta (Poleta) is responsible for efficient translesion synthesis (TLS) past cis-syn cyclobutane thymine dimers (TT dimers), the major DNA lesions induced by UV irradiation. PMID: 16824193
- Human DNA polymerase eta selectively produces a two-base deletion in copying the N2-guanyl adduct of 2-amino-3-methylimidazo[4,5-f]quinoline but not the C8 adduct at the NarI G3 site. PMID: 16835218
- The enzymatic reactions with human DNA polymerase eta on oxidative products of guanine and 8-oxoG are investigated. PMID: 17150533
- Evolutionary conservation of efficient T[CPD]T bypass by HsPoleta and AtPoleta may reflect a high degree of exposure of human skin and plants to solar UV-B radiation. PMID: 18366182
- When copying undamaged DNA, DNA polymerase theta generates single base errors at rates 10- to more than 100-fold higher than for other family A members. PMID: 18503084
- Domain mapping of the 98-kDa enzyme by limited proteolysis and NaBH(4) cross-linking with a base excision repair intermediate revealed that the dRP lyase active site resides in a 24-kDa domain of Pol theta. PMID: 19188258
Database Links
Involvement In Disease
Breast cancer (BC)
Protein Families
DNA polymerase type-A family
Subcellular Location
Nucleus. Chromosome.
Tissue Specificity
Highly expressed in testis.
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