Recognition of Damaged DNA for Nucleotide Excision Repair: A Correlated Motion Mechanism with a Mismatched cis-syn Thymine Dimer Lesion

Research output: Contribution to journalArticle

Abstract

Mammalian global genomic nucleotide excision repair requires lesion recognition by XPC, whose detailed binding mechanism remains to be elucidated. Here we have delineated the dynamic molecular pathway and energetics of lesion-specific and productive binding by the Rad4/yeast XPC lesion recognition factor, as it forms the open complex [Min, J. H., and Pavletich, N. P. (2007) Nature 449, 570-575; Chen, X., et al. (2015) Nat. Commun. 6, 5849] that is required for excision. We investigated extensively a cis-syn cyclobutane pyrimidine dimer in mismatched duplex DNA, using high-level computational approaches. Our results delineate a preferred correlated motion mechanism, which provides for the first time an atomistic description of the sequence of events as Rad4 productively binds to the damaged DNA. (Figure Presented).

Original languageEnglish (US)
Pages (from-to)5263-5267
Number of pages5
JournalBiochemistry
Volume54
Issue number34
DOIs
StatePublished - Sep 1 2015

Fingerprint

Pyrimidine Dimers
DNA Repair
Repair
Nucleotides
DNA
Molecular Dynamics Simulation
Yeast
Molecular dynamics
Yeasts

ASJC Scopus subject areas

  • Biochemistry

Cite this

@article{88f968c085f241b79200869d8e887918,
title = "Recognition of Damaged DNA for Nucleotide Excision Repair: A Correlated Motion Mechanism with a Mismatched cis-syn Thymine Dimer Lesion",
abstract = "Mammalian global genomic nucleotide excision repair requires lesion recognition by XPC, whose detailed binding mechanism remains to be elucidated. Here we have delineated the dynamic molecular pathway and energetics of lesion-specific and productive binding by the Rad4/yeast XPC lesion recognition factor, as it forms the open complex [Min, J. H., and Pavletich, N. P. (2007) Nature 449, 570-575; Chen, X., et al. (2015) Nat. Commun. 6, 5849] that is required for excision. We investigated extensively a cis-syn cyclobutane pyrimidine dimer in mismatched duplex DNA, using high-level computational approaches. Our results delineate a preferred correlated motion mechanism, which provides for the first time an atomistic description of the sequence of events as Rad4 productively binds to the damaged DNA. (Figure Presented).",
author = "Hong Mu and Nicholas Geacintov and Yingkai Zhang and Suse Broyde",
year = "2015",
month = "9",
day = "1",
doi = "10.1021/acs.biochem.5b00840",
language = "English (US)",
volume = "54",
pages = "5263--5267",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "34",

}

TY - JOUR

T1 - Recognition of Damaged DNA for Nucleotide Excision Repair

T2 - A Correlated Motion Mechanism with a Mismatched cis-syn Thymine Dimer Lesion

AU - Mu, Hong

AU - Geacintov, Nicholas

AU - Zhang, Yingkai

AU - Broyde, Suse

PY - 2015/9/1

Y1 - 2015/9/1

N2 - Mammalian global genomic nucleotide excision repair requires lesion recognition by XPC, whose detailed binding mechanism remains to be elucidated. Here we have delineated the dynamic molecular pathway and energetics of lesion-specific and productive binding by the Rad4/yeast XPC lesion recognition factor, as it forms the open complex [Min, J. H., and Pavletich, N. P. (2007) Nature 449, 570-575; Chen, X., et al. (2015) Nat. Commun. 6, 5849] that is required for excision. We investigated extensively a cis-syn cyclobutane pyrimidine dimer in mismatched duplex DNA, using high-level computational approaches. Our results delineate a preferred correlated motion mechanism, which provides for the first time an atomistic description of the sequence of events as Rad4 productively binds to the damaged DNA. (Figure Presented).

AB - Mammalian global genomic nucleotide excision repair requires lesion recognition by XPC, whose detailed binding mechanism remains to be elucidated. Here we have delineated the dynamic molecular pathway and energetics of lesion-specific and productive binding by the Rad4/yeast XPC lesion recognition factor, as it forms the open complex [Min, J. H., and Pavletich, N. P. (2007) Nature 449, 570-575; Chen, X., et al. (2015) Nat. Commun. 6, 5849] that is required for excision. We investigated extensively a cis-syn cyclobutane pyrimidine dimer in mismatched duplex DNA, using high-level computational approaches. Our results delineate a preferred correlated motion mechanism, which provides for the first time an atomistic description of the sequence of events as Rad4 productively binds to the damaged DNA. (Figure Presented).

UR - http://www.scopus.com/inward/record.url?scp=84940765357&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84940765357&partnerID=8YFLogxK

U2 - 10.1021/acs.biochem.5b00840

DO - 10.1021/acs.biochem.5b00840

M3 - Article

C2 - 26270861

AN - SCOPUS:84940765357

VL - 54

SP - 5263

EP - 5267

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 34

ER -