Human replication protein A can suppress the intrinsic in vitro mutator phenotype of human DNA polymerase lambda

Nucleic Acids Research
Giovanni MagaUlrich Hübscher

Abstract

DNA polymerase lambda (pol lambda) is a member of the X family DNA polymerases and is endowed with multiple enzymatic activities. In this work we investigated the in vitro miscoding properties of full-length, human pol lambda either in the absence or in the presence of the human auxiliary proteins proliferating cell nuclear antigen (PCNA) and replication protein A (RP-A). Our data suggested that (i) pol lambda had an intrinsic ability to create mismatches and to incorporate ribonucleotides at nearly physiological Mn++ and Mg++ concentrations; (ii) the sequence of the template-primer could influence the misincorporation frequency of pol lambda; (iii) pol lambda preferentially generated G:T and G:G mismatches; (iv) RP-A, but not PCNA, selectively prevented misincorporation of an incorrect nucleotide by pol lambda, without affecting correct incorporation and (v) this inhibitory effect required a precise ratio between the concentrations of pol lambda and RP-A. Possible physiological implications of these findings for the in vivo fidelity of pol lambda are discussed.

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Citations

Jul 27, 2007·Science in China. Series C, Life Sciences·Fu GuHong Lü
Dec 24, 2008·Proceedings of the National Academy of Sciences of the United States of America·Giovanni MagaUlrich Hübscher
Aug 29, 2006·Nucleic Acids Research·Ellen FanningAndrew R Nager
Nov 4, 2008·Biochemistry. Biokhimii︠a︡·Yu S KrasikovaO I Lavrik
Feb 17, 2009·Biochemistry. Biokhimii︠a︡·P E Pestryakov, O I Lavrik
Feb 5, 2011·Molekuliarnaia biologiia·E A Belousova, O I Lavrik
Mar 3, 2015·Chemical Research in Toxicology·Hiroyuki KamiyaHideyoshi Harashima
Sep 6, 2011·Current Opinion in Chemical Biology·Ulrich Hübscher, Giovanni Maga
Jan 22, 2009·The FEBS Journal·Kengo SakaguchiKazuki Iwabata
Feb 27, 2015·DNA Repair·E A Belousova, O I Lavrik
Mar 1, 2012·Cell Cycle·Enni MarkkanenBarbara van Loon
Jul 5, 2007·The Journal of Biological Chemistry·Ekaterina G Frank, Roger Woodgate
Mar 7, 2021·International Journal of Molecular Sciences·Elisa MentegariGiovanni Maga
Apr 29, 2010·Biochemistry·Ekaterina A BelousovaOlga I Lavrik

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Methods Mentioned

BETA
immunodepletion

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