HNPCC Mutations in the Human DNA Mismatch Repair Gene HMLH1 Influence Assembly of HMutLalpha and HMLH1-hEXO1 Complexes

Overview

Journal Oncogene

Specialties Molecular Biology
Oncology

Date 2001 Jun 29

PMID 11429708

Citations 29

Authors

A C Jager

M Rasmussen

H C Bisgaard

K K Singh

F C Nielsen

L J Rasmussen

Affiliations

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Abstract

Hereditary nonpolyposis colorectal cancer (HNPCC) is a common inherited form of neoplasia caused by germline mutations in DNA mismatch repair (MMR) genes. MMR proteins have been reported to associate with several proteins, including the human exonuclease 1 (hEXO1). We report here novel HNPCC-hMLH1 mutant proteins (T117M, Q426X and 1813insA) in Danish HNPCC patients. We demonstrate 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 hMutLalpha heterodimer assembly essential for MMR activity.

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