6cst
Structure of human DNA polymerase kappa with DNAStructure of human DNA polymerase kappa with DNA
Structural highlights
Function[POLK_HUMAN] DNA polymerase specifically involved in DNA repair. Plays an important role in translesion synthesis, where the normal high-fidelity DNA polymerases cannot proceed and DNA synthesis stalls. Depending on the context, it inserts the correct base, but causes frequent base transitions, transversions and frameshifts. Lacks 3'-5' proofreading exonuclease activity. Forms a Schiff base with 5'-deoxyribose phosphate at abasic sites, but does not have lyase activity.[1] [2] [3] [4] [5] [6] [7] Publication Abstract from PubMedHuman polymerase kappa (polkappa) is a distinct Y-family DNA polymerase with a unique N-terminal N-clasp domain. The N-clasp renders polkappa's high efficiency and accuracy in DNA replication and lesion bypass. How N-clasp empowers polkappa in replication remains unclear due to the disordering of N-clasp. Here, we present a 2.0-A resolution crystal structure of a polkappa ternary complex with DNA and an incoming nucleotide. The structure-function study reveals an ordered N-clasp domain that brings conserved and functionally important residues in contact with the replicating basepair in the active site and contributes to the nucleotidyl transfer reaction. Particularly, a fully ordered Lys25 from the N-clasp domain is in H-bonding with the alpha- and gamma-phosphates of the incoming nucleotide. K25A mutation reduces the polymerase activity of polkappa significantly. This lysine is structurally analogous to a conserved lysine in the A-family DNA polymerases in the closed form. In contrast, Lys25 in the previous structures of polkappa does not have any contacts with the incoming nucleotide, resembling an open form of a DNA polymerase. Based on structural and functional similarity, we propose a local open/closed mechanism for polkappa in DNA replication catalysis, which mimics the common mechanism for all DNA polymerases. 2.0 A resolution crystal structure of human polkappa reveals a new catalytic function of N-clasp in DNA replication.,Jha V, Ling H Sci Rep. 2018 Oct 11;8(1):15125. doi: 10.1038/s41598-018-33371-5. PMID:30310122[8] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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