6P1U
Post-catalytic nicked complex of human DNA Polymerase Mu with 1-nt gapped substrate containing template 8OG and newly incorporated CMP
Summary for 6P1U
| Entry DOI | 10.2210/pdb6p1u/pdb |
| Descriptor | DNA-directed DNA/RNA polymerase mu, 4-(2-HYDROXYETHYL)-1-PIPERAZINE ETHANESULFONIC ACID, 1,2-ETHANEDIOL, ... (12 entities in total) |
| Functional Keywords | family x polymerase, nhej, transferase |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 4 |
| Total formula weight | 46532.03 |
| 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 citation | Kaminski, 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: 31435651DOI: 10.1093/nar/gkz680 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.75 Å) |
Structure validation
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