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

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.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Maga G,Shevelev I,Villani G,Spadari S,Hübscher U

doi

10.1093/nar/gkl032

keywords:

subject

Has Abstract

pub_date

2006-03-06 00:00:00

pages

1405-15

issue

5

eissn

0305-1048

issn

1362-4962

pii

34/5/1405

journal_volume

34

pub_type

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