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Mol Cell
2009 Dec 25;366:1086-94. doi: 10.1016/j.molcel.2009.12.010.
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Nucleosome remodeling by hMSH2-hMSH6.
Javaid S
,
Manohar M
,
Punja N
,
Mooney A
,
Ottesen JJ
,
Poirier MG
,
Fishel R
.
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DNA nucleotide mismatches and lesions arise on chromosomes that are a complex assortment of protein and DNA (chromatin). The fundamental unit of chromatin is a nucleosome that contains approximately 146 bp DNA wrapped around an H2A, H2B, H3, and H4 histone octamer. We demonstrate that the mismatch recognition heterodimer hMSH2-hMSH6 disassembles a nucleosome. Disassembly requires a mismatch that provokes the formation of hMSH2-hMSH6 hydrolysis-independent sliding clamps, which translocate along the DNA to the nucleosome. The rate of disassembly is enhanced by actual or mimicked acetylation of histone H3 within the nucleosome entry-exit and dyad axis that occurs during replication and repair in vivo and reduces DNA-octamer affinity in vitro. Our results support a passive mechanism for chromatin remodeling whereby hMSH2-hMSH6 sliding clamps trap localized fluctuations in nucleosome positioning and/or wrapping that ultimately leads to disassembly, and highlight unanticipated strengths of the Molecular Switch Model for mismatch repair (MMR).
Acharya,
The coordinated functions of the E. coli MutS and MutL proteins in mismatch repair.
2003, Pubmed
Acharya,
The coordinated functions of the E. coli MutS and MutL proteins in mismatch repair.
2003,
Pubmed
Ataian,
Five repair pathways in one context: chromatin modification during DNA repair.
2006,
Pubmed
Boland,
Lynch syndrome: form, function, proteins, and basketball.
2005,
Pubmed
Constantin,
Human mismatch repair: reconstitution of a nick-directed bidirectional reaction.
2005,
Pubmed
Drummond,
Isolation of an hMSH2-p160 heterodimer that restores DNA mismatch repair to tumor cells.
1995,
Pubmed
Dupaigne,
Rad51 polymerization reveals a new chromatin remodeling mechanism.
2008,
Pubmed
English,
Structural basis for the histone chaperone activity of Asf1.
2006,
Pubmed
,
Xenbase
Escargueil,
What histone code for DNA repair?
2008,
Pubmed
Fang,
Human strand-specific mismatch repair occurs by a bidirectional mechanism similar to that of the bacterial reaction.
1993,
Pubmed
Flaus,
Sin mutations alter inherent nucleosome mobility.
2004,
Pubmed
Gangaraju,
Mechanisms of ATP dependent chromatin remodeling.
2007,
Pubmed
Gradia,
The human mismatch recognition complex hMSH2-hMSH6 functions as a novel molecular switch.
1997,
Pubmed
Gradia,
hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA.
1999,
Pubmed
Gradia,
The role of mismatched nucleotides in activating the hMSH2-hMSH6 molecular switch.
2000,
Pubmed
Groth,
Chromatin challenges during DNA replication and repair.
2007,
Pubmed
Haber,
Altering the conserved nucleotide binding motif in the Salmonella typhimurium MutS mismatch repair protein affects both its ATPase and mismatch binding activities.
1991,
Pubmed
Hyland,
Insights into the role of histone H3 and histone H4 core modifiable residues in Saccharomyces cerevisiae.
2005,
Pubmed
Jackson,
Deposition of newly synthesized histones: hybrid nucleosomes are not tandemly arranged on daughter DNA strands.
1988,
Pubmed
Kolodner,
Coupling distant sites in DNA during DNA mismatch repair.
2007,
Pubmed
Kruger,
Amino acid substitutions in the structured domains of histones H3 and H4 partially relieve the requirement of the yeast SWI/SNF complex for transcription.
1995,
Pubmed
Kurumizaka,
Sin mutations of histone H3: influence on nucleosome core structure and function.
1997,
Pubmed
,
Xenbase
Li,
Nucleosomes facilitate their own invasion.
2004,
Pubmed
,
Xenbase
Lowary,
New DNA sequence rules for high affinity binding to histone octamer and sequence-directed nucleosome positioning.
1998,
Pubmed
Luger,
Preparation of nucleosome core particle from recombinant histones.
1999,
Pubmed
,
Xenbase
Manohar,
Acetylation of histone H3 at the nucleosome dyad alters DNA-histone binding.
2009,
Pubmed
,
Xenbase
Mazurek,
Sequence context effect for hMSH2-hMSH6 mismatch-dependent activation.
2009,
Pubmed
Mendillo,
Analysis of the interaction between the Saccharomyces cerevisiae MSH2-MSH6 and MLH1-PMS1 complexes with DNA using a reversible DNA end-blocking system.
2005,
Pubmed
Muthurajan,
Crystal structures of histone Sin mutant nucleosomes reveal altered protein-DNA interactions.
2004,
Pubmed
Polach,
Mechanism of protein access to specific DNA sequences in chromatin: a dynamic equilibrium model for gene regulation.
1995,
Pubmed
Schofield,
Interaction of Escherichia coli MutS and MutL at a DNA mismatch.
2001,
Pubmed
Selmane,
Formation of a DNA mismatch repair complex mediated by ATP.
2003,
Pubmed
Sogo,
Structure of replicating simian virus 40 minichromosomes. The replication fork, core histone segregation and terminal structures.
1986,
Pubmed
Thåström,
Sequence motifs and free energies of selected natural and non-natural nucleosome positioning DNA sequences.
1999,
Pubmed
Thåström,
Measurement of histone-DNA interaction free energy in nucleosomes.
2004,
Pubmed
Utley,
In vitro analysis of transcription factor binding to nucleosomes and nucleosome disruption/displacement.
1996,
Pubmed
Yoshioka,
ATR kinase activation mediated by MutSalpha and MutLalpha in response to cytotoxic O6-methylguanine adducts.
2006,
Pubmed
Zhang,
Reconstitution of 5'-directed human mismatch repair in a purified system.
2005,
Pubmed
Zhang,
Identification of novel histone post-translational modifications by peptide mass fingerprinting.
2003,
Pubmed
