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6P1W

Pre-catalytic ternary complex of human DNA Polymerase Mu with 1-nt gapped substrate containing undamaged template dG and bound incoming CMPCPP

Summary for 6P1W
Entry DOI10.2210/pdb6p1w/pdb
DescriptorDNA-directed DNA/RNA polymerase mu, 1,2-ETHANEDIOL, DNA (5'-D(*CP*GP*GP*CP*GP*TP*AP*CP*G)-3'), ... (11 entities in total)
Functional Keywordsfamily x polymerase, nhej, transferase
Biological sourceHomo sapiens (Human)
More
Total number of polymer chains4
Total formula weight45978.59
Authors
Kaminski, A.M.,Pedersen, L.C.,Bebenek, K.,Chiruvella, K.K.,Ramsden, D.A.,Kunkel, T.A. (deposition date: 2019-05-20, release date: 2019-09-04, Last modification date: 2023-10-11)
Primary citationKaminski, A.M.,Chiruvella, K.K.,Ramsden, D.A.,Kunkel, T.A.,Bebenek, K.,Pedersen, L.C.
Unexpected behavior of DNA polymerase Mu opposite template 8-oxo-7,8-dihydro-2'-guanosine.
Nucleic Acids Res., 47:9410-9422, 2019
Cited by
PubMed Abstract: DNA double-strand breaks (DSBs) resulting from reactive oxygen species generated by exposure to UV and ionizing radiation are characterized by clusters of lesions near break sites. Such complex DSBs are repaired slowly, and their persistence can have severe consequences for human health. We have therefore probed DNA break repair containing a template 8-oxo-7,8-dihydro-2'-guanosine (8OG) by Family X Polymerase μ (Pol μ) in steady-state kinetics and cell-based assays. Pol μ tolerates 8OG-containing template DNA substrates, and the filled products can be subsequently ligated by DNA Ligase IV during Nonhomologous end-joining. Furthermore, Pol μ exhibits a strong preference for mutagenic bypass of 8OG by insertion of adenine. Crystal structures reveal that the template 8OG is accommodated in the Pol μ active site with none of the DNA substrate distortions observed for Family X siblings Pols β or λ. Kinetic characterization of template 8OG bypass indicates that Pol μ inserts adenosine nucleotides with weak sugar selectivity and, given the high cellular concentration of ATP, likely performs its role in repair of complex 8OG-containing DSBs using ribonucleotides.
PubMed: 31435651
DOI: 10.1093/nar/gkz680
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.751 Å)
Structure validation

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