Lynch syndrome is an autosomal dominant cancer predisposition syndrome which is caused by a germline mutation in one of four genes, MLH1, MSH2, MSH6 or PMS2. Individuals with a germline mutation in one of these genes are at increased lifetime risk of colon, endometrial, ovarian, small intestine, renal pelvis and ureter. Less commonly patients may develop biliary tract cancers, gastric and pancr...

Microsatellite instability (MSI) is observed in a subset of endometrial cancers (ECs) and is attributed to defects in mismatch repair. Mismatch repair deficiency allows for accumulation of mutations in the coding repeats of key target genes, which may be involved in the initiation and progression of MSI+ EC. We examined genes implicated in DNA repair pathways in 38 MSI-high (MSI-H), 10 MSI-low,...

Mismatch repair (MMR) is an evolutionarily conserved DNA repair system, which corrects mismatched bases arising during DNA replication. MutS recognizes and binds base pair mismatches, while the MutL protein interacts with MutS-mismatch complex and triggers MutH endonuclease activity at a distal-strand discrimination site on the DNA. The mechanism of communication between these two distal sites ...

We have studied the possible interactions between the mismatch repair system and p53 in a human colon cancer cell line, HCT-116 (known to have a homozygous mutation in mismatch repair gene hMLH1 on chromosome 3) and in a clone obtained after insertion of a single copy of chromosome 3 (HCT-116+ ch3). Loss of DNA mismatch repair activity resulted in resistance to cisplatin (DDP). p53 accumulated ...

Selection of cells for resistance to cisplatin, a well-recognized mutagen, could result in mutations in genes involved in DNA mismatch repair and thereby to resistance to DNA-alkylating agents. Parental cells of the human ovarian adenocarcinoma cell line 2008 expressed liMI.HI when analyzed with immunoblot. One subline selected for resistance to cisplatin (2008/A) expressed no hMLHl, whereas an...

Defects in DNA mismatch repair have been associated with both hereditary and sporadic forms of cancer. Recently, it has been shown that human cell lines deficient in mismatch repair were also defective in the transcription-coupled repair (TCR) of UV-induced DNA damage. We examined whether TCR of ionizing radiation-induced DNA damage also requires the genes involved in DNA mismatch repair. Cells...

1. Senescence is intimately connected with physiological state, which is affected by the environment. Two aspects of the environment – stress and caloric intake – are investigated in the context of senescence, particularly in the context of repair of damage caused by endogenous and exogenous stressors. 2. In a simple life-history model, the organism is characterized by size (affecting reproduct...

This paper reports reconstitution of 5'-nick-directed mismatch repair using purified human proteins. The reconstituted system includes MutSalpha or MutSbeta, MutLalpha, RPA, EXO1, HMGB1, PCNA, RFC, polymerase delta, and ligase I. In this system, MutSbeta plays a limited role in repair of base-base mismatches, but it processes insertion/deletion mispairs much more efficiently than MutSalpha, whi...