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Papers In Press, published online ahead of print May 22, 2001
NIDDK, NIH, Bethesda, MD 20892-1810
Corresponding Author: hsieh{at}ncifcrf.gov
Both MutS and MutL are required to activate downstream events in DNA mismatch repair. We examine the rate of dissociation of MutS from a mismatch using linear heteroduplex DNAs or heteroduplexes blocked at one or both ends by four-way DNA junctions in the presence and absence of MutL. In the presence of ATP, dissociation of MutS from linear heteroduplexes or heteroduplexes blocked at only one end occurs within 15 sec. When both duplex ends are blocked, MutS remains associated with the DNA in complexes with half-lives of 30 min. DNaseI footprinting of MutS complexes is consistent with migration of MutS throughout the DNA duplex region. When MutL is present, it associates with MutS and prevents ATP-dependent migration away from the mismatch in a manner that is dependent on the length of the heteroduplex. The rate and extent of mismatch-provoked cleavage at hemimethylated GATC sites by MutH in the presence of MutS, MutL and ATP are the same whether the mismatch and GATC sites are in cis or in trans. These results suggest that a MutS-MutL complex in the vicinity of a mismatch is involved in activating MutH.
J. Biol. Chem, 10.1074/jbc.M103148200
Submitted on April 9, 2001
Revised on May 18, 2001
Accepted on May 22, 2001
Interaction of MutS and MutL at a DNA mismatch
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