Sequence context effect for hMSH2-hMSH6 mismatch-dependent activation

Mazurek, A., Johnson, C. N., Germann, M. W., Fishel, R. (March 2009) Sequence context effect for hMSH2-hMSH6 mismatch-dependent activation. Proc Natl Acad Sci U S A, 106 (11). pp. 4177-4182.

[thumbnail of Paper]
PDF (Paper)
Mazurek PNAS 2009.pdf - Published Version

Download (659kB) | Preview
DOI: 10.1073/pnas.0808572106


Numerous DNA mismatches and lesions activate MutS homologue (MSH) ATPase activity that is essential for mismatch repair (MMR). We have found that a mismatch embedded in a nearest-neighbor sequence context containing symmetric 3'-purines (2 x 3'-purines) enhanced, whereas symmetric 3'-pyrimidines (2 x 3'-pyrimidines) reduced, hMSH2-hMSH6 ATPase activation. The 3'-purine/pyrimidine effect was most evident for G-containing mispairs. A similar trend pervaded mismatch binding (K(D)) and the melting of unbound oligonucleotides (T(m); DeltaG). However, these latter measures did not accurately predict the hierarchy of MSH ATPase activation. NMR studies of imino proton lifetime, solvent accessibility, and NOE connectivity suggest that sequence contexts that provoke improved MSH-activation displayed enhanced localized DNA flexibility: a dynamic DNA signature that may account for the wide range of lesions that activate MSH functions.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > small molecules > ATP
diseases & disorders > cancer
diseases & disorders
organism description > animal > mammal > primates > hominids > human
CSHL Authors:
Communities: CSHL labs > Stillman lab
CSHL Post Doctoral Fellows
Depositing User: Matt Covey
Date: 17 March 2009
Date Deposited: 20 Feb 2013 14:57
Last Modified: 08 Nov 2017 20:51
PMCID: PMC2657375
Related URLs:

Actions (login required)

Administrator's edit/view item Administrator's edit/view item
CSHL HomeAbout CSHLResearchEducationNews & FeaturesCampus & Public EventsCareersGiving