Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-5-18
pubmed:abstractText
7,8-Dihydro-8-oxoguanine (oxoG), the predominant oxidative DNA damage lesion, is processed differently by high-fidelity and Y-family lesion bypass polymerases. Although high-fidelity polymerases extend predominantly from an A base opposite an oxoG, the Y-family polymerases Dpo4 and human Pol eta preferentially extend from the oxoG*C base pair. We have determined crystal structures of extension Dpo4 ternary complexes with oxoG opposite C, A, G, or T and the next nascent base pair. We demonstrate that neither template backbone nor the architecture of the active site is perturbed by the oxoG(anti)*C and oxoG*A pairs. However, the latter manifest conformational heterogeneity, adopting both oxoG(syn)*A(anti) and oxoG(anti)*A(syn) alignment. Hence, the observed reduced primer extension from the dynamically flexible 3'-terminal primer base A is explained. Because of homology between Dpo4 and Pol eta, such a dynamic screening mechanism might be utilized by Dpo4 and Pol eta to regulate error-free versus error-prone bypass of oxoG and other lesions.
pubmed:grant
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0969-2126
pubmed:author
pubmed:issnType
Print
pubmed:day
13
pubmed:volume
17
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
725-36
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Impact of conformational heterogeneity of OxoG lesions and their pairing partners on bypass fidelity by Y family polymerases.
pubmed:affiliation
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural