Linked Life Data

21454642

Source:http://linkedlifedata.com/resource/pubmed/id/21454642

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
20
pubmed:dateCreated
2011-5-16
pubmed:abstractText
To counteract the deleterious effects of DNA damage, cells are equipped with specialized polymerases to bypass DNA lesions. Previous biochemical studies revealed that DinB family DNA polymerases, including Escherichia coli DNA polymerase IV and human DNA polymerase ?, efficiently incorporate the correct nucleotide opposite some N(2)-modified 2'-deoxyguanosine derivatives. Herein, we used shuttle vector technology and demonstrated that deficiency in Polk or Poli in mouse embryonic fibroblast (MEF) cells resulted in elevated frequencies of G?T and G?A mutations at N(2)-(1-carboxyethyl)-2'-deoxyguanosine (N(2)-CEdG) and N(2)-carboxymethyl-2'-deoxyguanosine (N(2)-CMdG) sites. Steady-state kinetic measurements revealed that human DNA polymerase ? preferentially inserts the correct nucleotide, dCMP, opposite N(2)-CEdG lesions. In contrast, no mutation was found after the N(2)-CEdG- and N(2)-CMdG-bearing plasmids were replicated in POLH-deficient human cells or Rev3-deficient MEF cells. Together, our results revealed that, in mammalian cells, both polymerases ? and ? are necessary for the error-free bypass of N(2)-CEdG and N(2)-CMdG. However, in the absence of polymerase ? or ?, other translesion synthesis polymerase(s) could incorporate nucleotide(s) opposite these lesions but would do so inaccurately.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1083-351X
pubmed:author
pubmed:copyrightInfo
© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.
pubmed:issnType
Electronic
pubmed:day
20
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
17503-11
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
The roles of DNA polymerases ? and ? in the error-free bypass of N2-carboxyalkyl-2'-deoxyguanosine lesions in mammalian cells.
pubmed:affiliation
From the Department of Chemistry, University of California, Riverside, California 92521, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural