The ability of proteins to locate specific targets among a vast excess of nonspecific DNA is a fundamental theme in biology. Basic principles governing these search mechanisms remain poorly understood, and no study has provided direct visualization of single proteins searching for and engaging target sites. Here we use the postreplicative mismatch repair proteins MutSα and MutLα as model system...

DNA synthesis and postreplication mismatch repair were measured in vitro using cell-free extracts from cultured human SY5Y neuroblastoma and WI38 fibroblast cells in different growth states. All extracts, including differentiated SY5Y and quiescent WI38 fibroblasts, catalyzed SV40 origin-dependent DNA synthesis, totally dependent on SV40 T-antigen. Thus, although differentiated neuroblastoma an...

The msh6 mismatch repair gene of Schizosaccharomyces pombe was cloned, sequenced, and inactivated. Strains bearing all combinations of inactivated msh6, msh2, and swi4 (the S. pombe MSH3 ortholog) alleles were tested for their defects in mitotic and meiotic mismatch repair. Mitotic mutation rates were similarly increased in msh6 and msh2 mutants, both for reversion of a base-base substitution a...

Half of hereditary nonpolyposis colon cancer kindreds harbor mutations that inactivate MutLa (MLH1 PMS2 heterodimer). MutLa is required for mismatch repair, but its function in this process is unclear. We show that human MutLa is a latent endonuclease that is activated in a mismatch-, MutSa-, RFC-, PCNA-, and ATP-dependent manner. Incision of a nicked mismatch-containing DNA heteroduplex by thi...

BACKGROUND Deficiency of DNA mismatch repair is a common feature of cancers exhibiting instability of microsatellite DNA sequences. Cancers with microsatellite instability are recognizable by their high rate of spontaneous frameshift mutations within microsatellite sequences, their resistance to killing by cytotoxic agents, and their localization to specific tissues, e.g., the proximal colon an...

1 Deparment of Gastrointestinal Surgery, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi 830011, Xinjiang, China 2 Infection & Statistical Office, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi 830011, Xinjiang, China 3 Department of Digestive Oncology, Affiliated Tumor Hospital, Xinjiang Medical University, Urumqi 830011, Xinjiang, China 4 Pathology Department, t...

Deoxyribosyl-dihydropyrimido[4,5-c][1,2]oxazin-7-one (dP) is a potent mutagenic deoxycytidine-derived base analogue capable of pairing with both A and G, thereby causing G. C --> A. T and A. T --> G. C transition mutations. We have found that the Escherichia coli DNA mismatch-repair system can protect cells against this mutagenic action. At a low dose, dP is much more mutagenic in mismatch-repa...

BACKGROUND Ovarian clear-cell carcinoma (OCC) is known to have a poor prognosis and selected genetic features of OCC remain unknown. We investigated microsatellite instability (MSI) and the expression of the DNA mismatch repair-related protein, p53. MATERIALS AND METHODS MSI was examined by polymerase chain reaction using mono-, di-, tri- and tetranucleotide repeat markers, and hMSH2, hMLH1, ...

Two methods were used in an attempt to increase the efficiency and strand selectivity of methyl-directed mismatch repair of bacteriophage lambda heteroduplexes in E. coli. Previous studies of such repair used lambda DNA that was only partially methylated as the source of methylated chains. Also, transfection was carried out in methylating strains. Either of these factors might have been respons...

Defects in genes involved in DNA mismatch repair have been detected in both hereditary and sporadic tumors of colon, endometrium, and ovary and suggested to be associated with tumorigenesis. To investigate disruptions of the mismatch repair system in hematological malignancies, we examined alterations of the human mutL homologue 1 (hMLH1) gene, a member of the mismatch repair gene family, in a ...