Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Patients with hereditary non-polyposis colorectal cancer (HNPCC) have germ-line mutations in one of four DNA mismatch repair genes (hMSH2, hMLH1, hPMS1 and hPMS2). It is supposed that a single functional copy of these genes is sufficient for normal mismatch repair, but it is not certain that this is the case under abnormal conditions such as rapid cell division or an increased tendency to DNA replication errors (RERs). We have analysed mismatch repair by examining replication errors in immortalised lymphoblastoid cells derived from two HNPCC patients heterozygous for mismatch repair defects (one hMSH2 mutant and one hMLH1 mutant), and from control individuals. Three conditions of cell culture have been used: (i) relatively slow cell growth and division; (ii) relatively fast growth and division; and (iii) chronic perturbation of the intracellular dNTP pool to promote a increased frequency of replication errors. No significant differences in microsatellite instability were found between HNPCC patients and controls in any of these environments. Lymphoblastoid cells from hMSH2 and hMLH1 mutant/wild-type heterozygotes appear, therefore, to have normal levels of mismatch repair, even under conditions that increase the requirement for repair. The pool bias cultures from the HNPCC patients and controls did, however, show similar, increased frequencies of RERs, suggesting that the mismatch repair capacity of the cells had been overloaded, but that the number of normal HNPCC alleles was not the limiting factor.

Type

Journal article

Journal

Mutat Res

Publication Date

12/03/1997

Volume

383

Pages

177 - 182

Keywords

Adaptor Proteins, Signal Transducing, Alleles, Carrier Proteins, Cell Division, Colorectal Neoplasms, Hereditary Nonpolyposis, DNA Repair, DNA Replication, DNA-Binding Proteins, Dinucleoside Phosphates, Humans, Leukocytes, Mononuclear, Microsatellite Repeats, MutL Protein Homolog 1, MutS Homolog 2 Protein, Neoplasm Proteins, Nuclear Proteins, Polymerase Chain Reaction, Proto-Oncogene Proteins, Tumor Cells, Cultured