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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
15
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pubmed:dateCreated |
2006-4-12
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pubmed:abstractText |
A central mystery in the function of site-specific DNA-binding proteins is the detailed mechanism for rapid location and binding of target sites in DNA. Human oxoguanine DNA glycosylase 1 (hOgg1), for example, must search out rare 8-oxoguanine lesions to prevent transversion mutations arising from oxidative stress. Here we report high-speed imaging of single hOgg1 enzyme molecules diffusing along DNA stretched by shear flow. Salt-concentration-dependent measurements reveal that such diffusion occurs as hOgg1 slides in persistent contact with DNA. At near-physiologic pH and salt concentration, hOgg1 has a subsecond DNA-binding time and slides with a diffusion constant as high as 5 x 10(6) bp(2)/s. Such a value approaches the theoretical upper limit for one-dimensional diffusion and indicates an activation barrier for sliding of only 0.5 kcal/mol (1 kcal = 4.2 kJ). This nearly barrierless Brownian sliding indicates that DNA glycosylases locate lesion bases by a massively redundant search in which the enzyme selectively binds 8-oxoguanine under kinetic control.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-10512846,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-10706276,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-10990792,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-11238177,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-11927259,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-11964263,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-12055620,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-12122472,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-12409465,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-12534293,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-12628933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-12947199,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-15178741,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-15196890,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-15465864,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-15469913,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-15525514,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-15588838,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-15800616,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-15939442,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-16243975,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-16248654,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-16461402,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-16497933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-1888726,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-380674,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-4612528,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-4924006,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-7317363,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-7846041,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-8248804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-8519772,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-8569504,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-8834810,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-9195879,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-9321410,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16585517-9929475
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0027-8424
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
103
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5752-7
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16585517-Amino Acid Substitution,
pubmed-meshheading:16585517-Bacteriophage lambda,
pubmed-meshheading:16585517-Binding Sites,
pubmed-meshheading:16585517-DNA, Viral,
pubmed-meshheading:16585517-DNA Damage,
pubmed-meshheading:16585517-DNA Glycosylases,
pubmed-meshheading:16585517-DNA Repair,
pubmed-meshheading:16585517-Guanine,
pubmed-meshheading:16585517-Humans,
pubmed-meshheading:16585517-Kinetics,
pubmed-meshheading:16585517-Microscopy, Fluorescence,
pubmed-meshheading:16585517-Models, Molecular,
pubmed-meshheading:16585517-Mutagenesis, Site-Directed,
pubmed-meshheading:16585517-Nucleic Acid Conformation,
pubmed-meshheading:16585517-Protein Conformation,
pubmed-meshheading:16585517-Recombinant Proteins,
pubmed-meshheading:16585517-Substrate Specificity
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pubmed:year |
2006
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pubmed:articleTitle |
A base-excision DNA-repair protein finds intrahelical lesion bases by fast sliding in contact with DNA.
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pubmed:affiliation |
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, MA 02138, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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