HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence assembly of hMutL alpha and hMLH1-hEXO1 complexes

Authors
Jager, AC Rasmussen, M Bisgaard, HC Singh, KK Nielsen, FC Rasmussen, LJ
Citation
Ac. Jager et al., HNPCC mutations in the human DNA mismatch repair gene hMLH1 influence assembly of hMutL alpha and hMLH1-hEXO1 complexes, ONCOGENE, 20(27), 2001, pp. 3590-3595
Citations number
30
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
09509232 → ACNP
Volume
20
Issue
27
Year of publication
2001
Pages
3590 - 3595
Database
ISI
SICI code
0950-9232(20010614)20:27<3590:HMITHD>2.0.ZU;2-B
Abstract
Hereditary nonpolyposis colorectal cancer (HNPCC) is common inherited form of neoplasia caused by germline mutations in DNA mismatch repair (MMR) gene s, MMR proteins have been reported to associate with several proteins, incl uding the human exonuclease 1 (hEXO1). We report here novel HNPCC-hMLH1 mut ant proteins (T117M, Q426X and 1813insA) in Danish HNPCC patients, We demon strate that these mutant HNPCC-hMLH1 proteins are unable to form complexes with hEXO1 and hPMS2 in vivo. The results indicate that mutations found in HNPCC gene carriers disrupt hMLH1 - hEXO1 complex formation and hMutL alpha heterodimer assembly essential for MMR activity.