Linked Life Data

21167175

Source:http://linkedlifedata.com/resource/pubmed/id/21167175

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2011-1-28
pubmed:databankReference
pubmed:abstractText
Abasic (apurinic/apyrimidinic) sites are among the most abundant DNA lesions in humans, and they present a strong block to replication. They are also highly mutagenic because when replicative DNA polymerases manage to insert a nucleotide opposite the lesion, they prefer to insert an A. Rev1, a member of Y-family DNA polymerases, does not obey the A-rule. This enzyme inserts a C opposite an abasic lesion with much greater catalytic efficiency than an A, G, or T. We present here the structure of yeast Rev1 in ternary complex with DNA containing an abasic lesion and with dCTP as the incoming nucleotide. The structure reveals a mechanism of synthesis across an abasic lesion that differs from that in other polymerases. The lesion is driven to an extrahelical position, and the incorporation of a C is mediated by an arginine (Arg324) that is conserved in all known orthologs of Rev1, including humans. The hydrophobic cavity that normally accommodates the unmodified G is instead filled with water molecules. Since Gs are especially prone to depurination through a spontaneous hydrolysis of the glycosidic bond, the ability of Rev1 to stabilize an abasic lesion in its active site and employ a surrogate arginine to incorporate a C provides a unique means for the "error-free" bypass of this noninstructional lesion.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1089-8638
pubmed:author
pubmed:copyrightInfo
Copyright © 2010. Published by Elsevier Ltd.
pubmed:issnType
Electronic
pubmed:day
11
pubmed:volume
406
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18-28
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
DNA synthesis across an abasic lesion by yeast REV1 DNA polymerase.
pubmed:affiliation
Department of Structural and Chemical Biology, Mount Sinai School of Medicine, Box 1677, 1425 Madison Avenue, New York, NY 10029, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural