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Post-catalytic complex of human Polymerase Mu (G433A) mutant with incoming UTP
Structural highlights
FunctionDPOLM_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.[1] [2] [3] [4] Publication Abstract from PubMedWhile most DNA polymerases discriminate against ribonucleotide triphosphate (rNTP) incorporation very effectively, the Family X member DNA polymerase mu (Pol mu) 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 mu with a ribonucleotide bound at the active site. These structures reveal that Pol mu 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 mu 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 mu 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. Structural accommodation of ribonucleotide incorporation by the DNA repair enzyme polymerase Mu.,Moon AF, Pryor JM, Ramsden DA, Kunkel TA, Bebenek K, Pedersen LC Nucleic Acids Res. 2017 Sep 6;45(15):9138-9148. doi: 10.1093/nar/gkx527. PMID:28911097[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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