7kth
From Proteopedia
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== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/DPOLM_HUMAN DPOLM_HUMAN] Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.<ref>PMID:12640116</ref> <ref>PMID:12888504</ref> <ref>PMID:17483519</ref> <ref>PMID:17915942</ref> | [https://www.uniprot.org/uniprot/DPOLM_HUMAN DPOLM_HUMAN] Gap-filling polymerase involved in repair of DNA double-strand breaks by non-homologous end joining (NHEJ). Participates in immunoglobulin (Ig) light chain gene rearrangement in V(D)J recombination.<ref>PMID:12640116</ref> <ref>PMID:12888504</ref> <ref>PMID:17483519</ref> <ref>PMID:17915942</ref> | ||
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| - | == Publication Abstract from PubMed == | ||
| - | Oxidized dGTP (8-oxo-7,8-dihydro-2 -deoxyguanosine triphosphate, 8-oxodGTP) insertion by DNA polymerases strongly promotes cancer and human disease. How DNA polymerases discriminate against oxidized and undamaged nucleotides, especially in error-prone double strand break (DSB) repair, is poorly understood. High-resolution time-lapse X-ray crystallography snapshots of DSB repair polymerase mu undergoing DNA synthesis reveal that a third active site metal promotes insertion of oxidized and undamaged dGTP in the canonical anti-conformation opposite template cytosine. The product metal bridged O8 with product oxygens, and was not observed in the syn-conformation opposite template adenine (At). Rotation of At into the syn-conformation enabled undamaged dGTP misinsertion. Exploiting metal and substrate dynamics in a rigid active site allows 8-oxodGTP to circumvent polymerase fidelity safeguards to promote pro-mutagenic double strand break repair. | ||
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| - | Watching a double strand break repair polymerase insert a pro-mutagenic oxidized nucleotide.,Jamsen JA, Sassa A, Shock DD, Beard WA, Wilson SH Nat Commun. 2021 Apr 6;12(1):2059. doi: 10.1038/s41467-021-21354-6. PMID:33824325<ref>PMID:33824325</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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| - | <div class="pdbe-citations 7kth" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
DNA Polymerase Mu, 8-oxodGTP:Ct Product State Ternary Complex, 10 mM Mg2+ (2160min)
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