An Alternative Pathway in Colorectal Carcinogenesis Based on the Mismatch Repair System and p53 Expression in Korean Patients with Sporadic Colorectal Cancer

2012 ◽  
Vol 20 (12) ◽  
pp. 4031-4040 ◽  
Author(s):  
Hyoung Ran Kim ◽  
Hee Cheol Kim ◽  
Hae-Ran Yun ◽  
Seok Hyung Kim ◽  
Cheol Keun Park ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Alternative Pathway ◽  
Colorectal Carcinogenesis ◽  
Sporadic Colorectal Cancer ◽  
Repair System ◽  
P53 Expression ◽  
Korean Patients ◽  
Mismatch Repair System

scholarly journals Mismatch Repair Processing of Carcinogen-DNA Adducts Triggers Apoptosis

1999 ◽  
Vol 19 (12) ◽  
pp. 8292-8301 ◽  
Author(s):  
Jianxin Wu ◽  
Liya Gu ◽  
Huixian Wang ◽  
Nicholas E. Geacintov ◽  
Guo-Min Li
Keyword(s):  
Dna Damage ◽  
Mismatch Repair ◽  
Repair System ◽  
Apoptotic Response ◽  
Chemical Carcinogens ◽  
P53 Expression ◽  
Dna Mismatch ◽  
Repair Deficiency ◽  
Mismatch Repair System

ABSTRACT The DNA mismatch repair pathway is well known for its role in correcting biosynthetic errors of DNA replication. We report here a novel role for mismatch repair in signaling programmed cell death in response to DNA damage induced by chemical carcinogens. Cells proficient in mismatch repair were highly sensitive to the cytotoxic effects of chemical carcinogens, while cells defective in either human MutS or MutL homologs were relatively insensitive. Since wild-type cells but not mutant cells underwent apoptosis upon treatment with chemical carcinogens, the apoptotic response is dependent on a functional mismatch repair system. By analyzing p53 expression in several pairs of cell lines, we found that the mismatch repair-dependent apoptotic response was mediated through both p53-dependent and p53-independent pathways. In vitro biochemical studies demonstrated that the human mismatch recognition proteins hMutSα and hMutSβ efficiently recognized DNA damage induced by chemical carcinogens, suggesting a direct participation of mismatch repair proteins in mediating the apoptotic response. Taken together, these studies further elucidate the mechanism by which mismatch repair deficiency predisposes to cancer, i.e., the deficiency not only causes a failure to repair mismatches generated during DNA metabolism but also fails to direct damaged and mutation-prone cells to commit suicide.

scholarly journals Deficient mismatch repair system in patients with sporadic advanced colorectal cancer

2009 ◽  
Vol 100 (2) ◽  
pp. 266-273 ◽  
Author(s):  
M Koopman ◽  
G A M Kortman ◽  
L Mekenkamp ◽  
M J L Ligtenberg ◽  
N Hoogerbrugge ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Advanced Colorectal Cancer ◽  
Repair System ◽  
Mismatch Repair System ◽  
Deficient Mismatch Repair

The Genetics of Hereditary Non-Polyposis Colorectal Cancer

2003 ◽  
Vol 1 (1) ◽  
pp. 137-144 ◽  
Author(s):  
Stephen B. Gruber ◽  
Wendy Kohlmann
Keyword(s):  
Colorectal Cancer ◽  
Microsatellite Instability ◽  
Mismatch Repair ◽  
Molecular Diagnostic ◽  
Repair System ◽  
Molecular Fingerprint ◽  
Dna Mismatch ◽  
Repair Protein ◽  
Mismatch Repair System ◽  
Defective Mismatch Repair

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominant condition accounting for 3% to 5% of all colorectal cancer. HNPCC is caused by germline mutations in the mismatch repair system and is recognized by a characteristic clinical phenotype as well as a hallmark of the tumors termed “microsatellite instability.” Microsatellite instability serves as a molecular fingerprint for defective mismatch repair and has proven to be useful in the molecular diagnostic workup for HNPCC. The crystal structure of the DNA mismatch repair protein MutS has been solved, providing insight into the molecular basis of defective mismatch repair. Genetic testing has become a key component of the treatment of patients and families with HNPCC, and enhanced surveillance for HNPCC has been shown to reduce the rate of colorectal cancer by more than half and improve 10-year survival from 68% to 93%.

Frequency of Defective Mismatch Repair System in a Series of Consecutive Cases of Colorectal Cancer in a National Cancer Center

2018 ◽  
Vol 49 (3) ◽  
pp. 379-384 ◽  
Author(s):  
Patricia E. López-Correa ◽  
Leonardo S. Lino-Silva ◽  
Armando Gamboa-Domínguez ◽  
César Zepeda-Najar ◽  
Rosa A. Salcedo-Hernández
Keyword(s):  
Colorectal Cancer ◽  
Mismatch Repair ◽  
Cancer Center ◽  
Repair System ◽  
Mismatch Repair System ◽  
Defective Mismatch Repair

Functional Specifics of the MutL Protein of the DNA Mismatch Repair System in Different Organisms

2020 ◽  
Vol 46 (6) ◽  
pp. 875-890
Author(s):  
M. V. Monakhova ◽  
M. A. Milakina ◽  
R. M. Trikin ◽  
T. S. Oretskaya ◽  
E. A. Kubareva
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Dna Mismatch ◽  
Dna Mismatch Repair System ◽  
Mismatch Repair System

scholarly journals Poorly Repaired Mismatches in Heteroduplex DNA are Hyper-Recombinagenic in Saccharomyces cerevisiae

Genetics ◽  
1996 ◽  
Vol 142 (2) ◽  
pp. 407-416 ◽  
Author(s):  
P Manivasakam ◽  
Susan M Rosenberg ◽  
P J Hastings
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Mismatch Repair ◽  
Genetic Markers ◽  
Meiotic Recombination ◽  
Repair System ◽  
Normal Allele ◽  
Heteroduplex Dna ◽  
Mismatch Repair System ◽  
Postmeiotic Segregation ◽  
System Operating

Abstract In yeast meiotic recombination, alleles used as genetic markers fall into two classes as regards their fate when incorporated into heteroduplex DNA. Normal alleles are those that form heteroduplexes that are nearly always recognized and corrected by the mismatch repair system operating in meiosis. High PMS (postmeiotic segregation) alleles form heteroduplexes that are inefficiently mismatch repaired. We report that placing any of several high PMS alleles very close to normal alleles causes hyperrecombination between these markers. We propose that this hyperrecombination is caused by the high PMS allele blocking a mismatch repair tract initiated from the normal allele, thus preventing corepair of the two alleles, which would prevent formation of recombinants. The results of three point crosses involving two PMS alleles and a normal allele suggest that high PMS alleles placed between two alleles that are normally corepaired block that corepair.

scholarly journals Saturation of DNA Mismatch Repair and Error Catastrophe by a Base Analogue in Escherichia coli

Genetics ◽  
2002 ◽  
Vol 161 (4) ◽  
pp. 1363-1371
Author(s):  
Kazuo Negishi ◽  
David Loakes ◽  
Roel M Schaaper
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Mutagenic Action ◽  
Wild Type ◽  
Dna Mismatch ◽  
Cell Counts ◽  
Error Catastrophe ◽  
Mismatch Repair System

Abstract 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-repair-defective mutH, mutL, and mutS strains than in a wild-type strain. At higher doses, the difference between the wild-type and the mutator strains becomes small, indicative of saturation of mismatch repair. Introduction of a plasmid containing the E. coli mutL+ gene significantly reduces dP-induced mutagenesis. Together, the results indicate that the mismatch-repair system can remove dP-induced replication errors, but that its capacity to remove dP-containing mismatches can readily be saturated. When cells are cultured at high dP concentration, mutant frequencies reach exceptionally high levels and viable cell counts are reduced. The observations are consistent with a hypothesis in which dP-induced cell killing and growth impairment result from excess mutations (error catastrophe), as previously observed spontaneously in proofreading-deficient mutD (dnaQ) strains.

Sign in / Sign up

Export Citation Format

Share Document