Human DNA mismatch repair: coupling of mismatch recognition to strand-specific excision.

Human DNA mismatch repair: coupling of mismatch recognition to strand-specific excision. Research Abstract Details 

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Human DNA mismatch repair: coupling of mismatch recognition to strand-specific excision. Abstract Text:

Huixian Wang,John B Hays,Huixian Wang,John B Hays,

Eukaryotic mismatch-repair (MMR) proteins MutSalpha and MutLalpha couple recognition of base mismatches to strand-specific excision, initiated in vivo at growing 3' ends and 5' Okazaki-fragment ends or, in human nuclear extracts, at nicks in exogenous circular substrates. We addressed five biochemical questions relevant to coupling models. Excision remained fully efficient at DNA:MutSalpha ratios of nearly 1 to 1 at various mismatch-nick distances, suggesting a requirement for only one MutSalpha molecule per substrate. As the mismatch-nick DNA contour distance D in exogenous substrates increased from 0.26 to 0.98 kbp, initiation of excision in extracts decreased as D(-0.43) rather than the D(-1) to D(-2) predicted by some translocation or diffusion models. Virtually all excision was along the shorter (3'-5') nick-mismatch, even when the other (5'-3') path was less than twice as long. These observations argue against stochastically directed translocating/diffusing recognition complexes. The failure of mismatched DNA in trans to provoke excision of separate nicked homoduplexes argues against one-stage (concerted) triggering of excision initiation by recognition complexes acting through space. However, proteins associated with gapped DNA did appear to compete in trans with those in cis to mismatch-associated proteins. Thus, as in Escherichia coli, eukaryotic MMR may involve distinct initial-activation and excision-path-commitment stages.

Human DNA mismatch repair: coupling of mismatch recognition to strand-specific excision. Publishing Authors By Initials

H Wang,JB Hays,H Wang,JB Hays,

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Human DNA mismatch repair: coupling of mismatch recognition to strand-specific excision. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Nucleic acids research

VOLUME: 35

Page Numbers: 6727-39

Journal Abbreviation: Nucleic Acids Res.

ISSN: 1362-4962

DAY: 4

MONTH: 10

YEAR: 2007

Human DNA mismatch repair: coupling of mismatch recognition to strand-specific excision. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Human DNA mismatch repair: coupling of mismatch recognition to strand-specific excision.

AFFILIATION: Department of Environmental and Molecular Toxicology, Oregon State University, Corvallis, OR 97331-7301, USA.

Country: England

AGENCY: United States NIEHS

GRANT: ES009848

ACRONYM: ES

MEDLINETA: Nucleic Acids Res

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