Dissociation of mismatch recognition and ATPase activity by hMSH2-hMSH3

Citation
T. Wilson et al., Dissociation of mismatch recognition and ATPase activity by hMSH2-hMSH3, J BIOL CHEM, 274(31), 1999, pp. 21659-21664
Citations number
44
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
274
Issue
31
Year of publication
1999
Pages
21659 - 21664
Database
ISI
SICI code
0021-9258(19990730)274:31<21659:DOMRAA>2.0.ZU;2-R
Abstract
MSH2-MSH3 directs the repair of insertion/deletion loops of up to 13 nucleo tides in vivo and in vitro, To examine the biochemical basis of this repair specificity, we characterized the mispair binding and ATPase activity of h MSH2-hMSH3. The ATPase was found to be regulated by a mismatch-stimulated A DP --> ATP exchange, which induces a conformational transition by the prote in complex. We demonstrated strong binding of hMSH2-hMSH3 to an insertion/d eletion loop containing 24 nucleotides that is incapable of provoking ADP - -> ATP exchange, suggesting that mismatch recognition appears to be necessa ry but not sufficient to induce the intrinsic ATPase. These studies support the idea that hMSH2-hMSH3 functions as an adenosine nucleotide-regulated m olecular switch that must be activated by mismatched nucleotides for classi cal mismatch repair to occur.