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MutS mediates heteroduplex loop formation by a translocation mechanism
Author(s) -
Allen Dwayne J.,
Makhov Alexander,
Grilley Michelle,
Taylor John,
Thresher Randy,
Modrich Paul,
Griffith Jack D.
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.14.4467
Subject(s) - biology , heteroduplex , chromosomal translocation , mechanism (biology) , microbiology and biotechnology , genetics , loop (graph theory) , biophysics , dna , gene , mathematics , combinatorics , philosophy , epistemology
Interaction of Escherichia coli MutS and MutL with heteroduplex DNA has been visualized by electron microscopy. In a reaction dependent on ATP hydrolysis, complexes between a MutS dimer and a DNA heteroduplex are converted to protein‐stabilized, α‐shaped loop structures with the mismatch in most cases located within the DNA loop. Loop formation depends on ATP hydrolysis and loop size increases linearly with time at a rate of 370 base pairs/min in phosphate buffer and about 10 000 base pairs/min in the HEPES buffer used for repair assay. These observations suggest a translocation mechanism in which a MutS dimer bound to a mismatch subsequently leaves this site by ATP‐dependent tracking or unidimensional movement that is in most cases bidirectional from the mispair. In view of the bidirectional capability of the methyl‐directed pathway, this reaction may play a role in determination of heteroduplex orientation. The rate of MutS‐mediated DNA loop growth is enhanced by MutL, and when both proteins are present, both are found at the base of α‐loop structures, and both can remain associated with excision intermediates produced in later stages of the reaction.