4x0q
Ternary complex of human DNA polymerase theta C-terminal domain binding ddGTP opposite dCMPTernary complex of human DNA polymerase theta C-terminal domain binding ddGTP opposite dCMP
Structural highlights
FunctionDPOLQ_HUMAN Has a DNA polymerase activity on nicked double-stranded DNA and on a singly primed DNA template. The enzyme activity is resistant to aphidicolin, and inhibited by dideoxynucleotides. Exhibites a single-stranded DNA-dependent ATPase activity. Could be involved in the repair of interstrand cross-links.[1] Publication Abstract from PubMedDNA polymerase theta protects against genomic instability via an alternative end-joining repair pathway for DNA double-strand breaks. Polymerase theta is overexpressed in breast, lung and oral cancers, and reduction of its activity in mammalian cells increases sensitivity to double-strand break-inducing agents, including ionizing radiation. Reported here are crystal structures of the C-terminal polymerase domain from human polymerase theta, illustrating two potential modes of dimerization. One structure depicts insertion of ddATP opposite an abasic-site analog during translesion DNA synthesis. The second structure describes a cognate ddGTP complex. Polymerase theta uses a specialized thumb subdomain to establish unique upstream contacts to the primer DNA strand, including an interaction with the 3'-terminal phosphate from one of five distinctive insertion loops. These observations demonstrate how polymerase theta grasps the primer to bypass DNA lesions or extend poorly annealed DNA termini to mediate end-joining. Human DNA polymerase theta grasps the primer terminus to mediate DNA repair.,Zahn KE, Averill AM, Aller P, Wood RD, Doublie S Nat Struct Mol Biol. 2015 Mar 16. doi: 10.1038/nsmb.2993. PMID:25775267[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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