Defective mismatch repair in extracts of colorectal and endometrial cancer cell lines exhibiting microsatellite instability.

摘要: A replication error (RER+) phenotype, characterized by somatic instability in simple repeated sequences, is associated with several types of cancer. To determine if a defect DNA fidelity or repair errors might explain this instability, we compared both processes cell-free extracts from RER+ endometrial and colorectal cancer cell lines to RER- lines. SV40 origin-dependent microsatellite sequence highly accurate regardless their RER phenotype. However, are defective mismatch repair, while not. Lack was observed when the signal (a nick) for strand-specific either 3' 5' mispair. One line contained deletions alleles putative gene hMSH2, one 4-base pair duplication hMSH2 allele. No mutation detected other allele five Repair readily each mixed repair-proficient extract, demonstrating that no trans-acting inhibitor present. Attempts complement deficiencies mixing two different identified three combinations restored repair. The data suggest that: (i) and, extrapolation, cancer; (ii) mutations gene, possibly genes, result repair; (iii) defect(s) these likely involves pre-incision events excision step, but not incision, polymerization, ligation steps; (iv) at least four functional complementation groups may be involved human