Source:http://linkedlifedata.com/resource/pubmed/id/19446528
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2009-5-18
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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.
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pubmed:grant |
http://linkedlifedata.com/resource/pubmed/grant/CA28038,
http://linkedlifedata.com/resource/pubmed/grant/CA46533,
http://linkedlifedata.com/resource/pubmed/grant/CA75449,
http://linkedlifedata.com/resource/pubmed/grant/CA99194,
http://linkedlifedata.com/resource/pubmed/grant/F32 GM069152,
http://linkedlifedata.com/resource/pubmed/grant/RR-15301
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pubmed:commentsCorrections | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0969-2126
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
17
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
725-36
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pubmed:meshHeading |
pubmed-meshheading:19446528-Base Pairing,
pubmed-meshheading:19446528-Base Sequence,
pubmed-meshheading:19446528-Binding Sites,
pubmed-meshheading:19446528-Crystallography, X-Ray,
pubmed-meshheading:19446528-DNA,
pubmed-meshheading:19446528-DNA Damage,
pubmed-meshheading:19446528-DNA Polymerase beta,
pubmed-meshheading:19446528-DNA Repair,
pubmed-meshheading:19446528-Guanine,
pubmed-meshheading:19446528-Molecular Sequence Data,
pubmed-meshheading:19446528-Nucleic Acid Conformation,
pubmed-meshheading:19446528-Protein Conformation
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pubmed:year |
2009
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pubmed:articleTitle |
Impact of conformational heterogeneity of OxoG lesions and their pairing partners on bypass fidelity by Y family polymerases.
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pubmed:affiliation |
Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
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