5VZ9

Post-catalytic complex of human Polymerase Mu (G433A) mutant with incoming dTTP

Summary for 5VZ9

• Entry DOI: 10.2210/pdb5vz9/pdb
• Related: 5TWP 5TWQ 5TWR 5TWS
• Descriptor: DNA-directed DNA/RNA polymerase mu, DNA (5'-D(*CP*GP*GP*CP*AP*TP*AP*CP*G)-3'), DNA (5'-D(*CP*GP*TP*AP*T)-3'), ... (10 entities in total)
• Functional Keywords: family x, nonhomologous end-joining, dna double strand break repair, ribonucleotide incorporation, transferase-dna complex, transferase/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 4
• Total formula weight: 46022.19

Authors

Moon, A.F.,Pryor, J.M.,Ramsden, D.A.,Kunkel, T.A.,Bebenek, K.,Pedersen, L.C. (deposition date: 2017-05-27, release date: 2017-07-05, Last modification date: 2023-10-04)

Primary citation

Moon, A.F.,Pryor, J.M.,Ramsden, D.A.,Kunkel, T.A.,Bebenek, K.,Pedersen, L.C.
Structural accommodation of ribonucleotide incorporation by the DNA repair enzyme polymerase Mu.
Nucleic Acids Res., 45:9138-9148, 2017

PubMed Abstract: While most DNA polymerases discriminate against ribonucleotide triphosphate (rNTP) incorporation very effectively, the Family X member DNA polymerase μ (Pol μ) incorporates rNTPs almost as efficiently as deoxyribonucleotides. To gain insight into how this occurs, here we have used X-ray crystallography to describe the structures of pre- and post-catalytic complexes of Pol μ with a ribonucleotide bound at the active site. These structures reveal that Pol μ binds and incorporates a rNTP with normal active site geometry and no distortion of the DNA substrate or nucleotide. Moreover, a comparison of rNTP incorporation kinetics by wildtype and mutant Pol μ indicates that rNTP accommodation involves synergistic interactions with multiple active site residues not found in polymerases with greater discrimination. Together, the results are consistent with the hypothesis that rNTP incorporation by Pol μ is advantageous in gap-filling synthesis during DNA double strand break repair by nonhomologous end joining, particularly in nonreplicating cells containing very low deoxyribonucleotide concentrations.

PubMed: 28911097
DOI: 10.1093/nar/gkx527

Experimental method

X-RAY DIFFRACTION (1.65 Å)