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DNA Repair System (dna + repair_system)
Selected AbstractsTime-course Expression of DNA Repair-related Genes in Hepatocytes of Zebrafish (Danio rerio) After UV-B ExposurePHOTOCHEMISTRY & PHOTOBIOLOGY, Issue 1 2009Juliana Z. Sandrini The objective of this study was to evaluate the time-course effects of UV-B exposure on expression of genes involved in the DNA repair system of zebrafish (Danio rerio) hepatocytes, a highly competent species in terms of damage repair induced by UV radiation. For gene expression analysis (RT-PCR), cells were exposed to 23.3 mJ cm,2 UV-B, which was the dose that affected viable cell number (reduction of 30% when compared with the control group) and produced no visual alteration on cell morphology. The early response observed (6 h) showed induction in the expression of the CDKI gene (cyclin-dependent kinase inhibitor) and genes related to DNA damage repair (mainly XPC and DDB2), while the late response observed (24 h) was more related to up-regulation of p53 and genes involved in cell cycle arrest (gadd45a, cyclinG1). In all times analyzed, the anti-apoptotic gene Bcl-2 was down-regulated. Another interesting result observed was the up-regulation of the Apex- 1 gene after UV-B exposure, which could indicate the induction of oxidative lesions in the DNA molecule. In conclusion, these results demonstrate an activation of the DNA repair system in hepatocytes of zebrafish exposed to UV-B radiation, mainly involving the participation of p53. [source] DNA repair dysfunction in gastrointestinal tract cancersCANCER SCIENCE, Issue 3 2008Yoshihiko Maehara The DNA repair system surveys the genome, which is always suffering from exposure to both exogenous as well as endogenous mutagens, to maintain the genetic information. The fact that the basis of this DNA repair system is highly conserved, from prokaryote to mammalian cells, suggests the importance of precise genome maintenance mechanisms for organisms. In the past 15 years, considerable progress has been made in understanding how repair processes interact and how disruptions of these mechanisms lead to the accumulation of mutations and carcinogenesis. In 1993, two groups reported that DNA mismatch repair could be associated with hereditary non-polyposis colorectal cancer, indicating a connection between faulty DNA repair function and cancer. More recently, an inherited disorder of DNA glycosylase, which removes mutagenic oxidized base from DNA, has been reported in individuals with a predisposition to multiple colorectal adenomas and carcinomas. This is the first report that directly indicates the role of the repair of oxidative DNA in human inherited cancer. Studies from gene knockout mice have elucidated the principal role of these repair systems in the process of carcinogenesis. Moreover, clinical samples derived from cancer patients have shown the direct involvement. This review focuses on the function of DNA mismatch repair and oxidative DNA/nucleotide repair among various DNA repair systems in cells, both of which are essentially involved in the carcinogenesis of gastrointestinal tract cancer. (Cancer Sci 2008; 99: 451,458) [source] DNA repair and cancer: Lessons from mutant mouse modelsCANCER SCIENCE, Issue 2 2004Takatoshi Ishikawa DNA damage, if the repair process, especially nucleotide excision repair (NER), is compromised or the lesion is repaired by some other error-prone mechanism, causes mutation and ultimately contributes to neoplastic transformation. Impairment of components of the DNA damage response pathway (e.g., p53) is also implicated in carcinogenesis. We currently have considerable knowledge of the role of DNA repair genes as tumor suppressors, both clinically and experimentally. The deleterious clinical consequences of inherited defects in DNA repair system are apparent from several human cancer predisposition syndromes (e.g., NER-compromised xeroderma pigmentosum [XP] and p53 -deficient Li-Fraumeni syndrome). However, experimental studies to support the clinical evidence are hampered by the lack of powerful animal models. Here, we review in vivo experimental data suggesting the protective function of DNA repair machinery in chemical carcinogenesis. We specifically focus on the three DNA repair genes, O6 -methylguanine-DNA methyltransferase gene (MGMT), XP group A gene (XPA) and p53. First, mice overexpressing MGMT display substantial resistance to nitrosamine-induced hepatocarcinogenesis. In addition, a reduction of spontaneous liver tumors and longer survival times were evident. However, there are no known mutations in the human MGMT and therefore no associated cancer syndrome. Secondly, XPA mutant mice are indeed prone to spontaneous and carcinogen-induced tumorigenesis in internal organs (which are not exposed to sunlight). The concomitant loss of p53 resulted in accelerated onset of carcinogenesis. Finally, p53 null mice are predisposed to brain tumors upon transplacental exposure to a carcinogen. Accumulated evidence in these three mutant mouse models firmly supports the notion that the DNA repair system is vital for protection against cancer. [source] Stationary phase mutagenesis: mechanisms that accelerate adaptation of microbial populations under environmental stressENVIRONMENTAL MICROBIOLOGY, Issue 10 2003Maia Kivisaar Summary Microorganisms are exposed to constantly changing environmental conditions. In a growth-restricting environment (e.g. during starvation), mutants arise that are able to take over the population by a process known as stationary phase mutation. Genetic adaptation of a microbial population under environmental stress involves mechanisms that lead to an elevated mutation rate. Under stressful conditions, DNA synthesis may become more erroneous because of the induction of error-prone DNA polymerases, resulting in a situation in which DNA repair systems are unable to cope with increasing amounts of DNA lesions. Transposition may also increase genetic variation. One may ask whether the rate of mutation under stressful conditions is elevated as a result of malfunctioning of systems responsible for accuracy or are there specific mechanisms that regulate the rate of mutations under stress. Evidence for the presence of mutagenic pathways that have probably been evolved to control the mutation rate in a cell will be discussed. [source] XRCC4 codon 247*A and XRCC4 promoter ,1394*T related genotypes but not XRCC4 intron 3 gene polymorphism are associated with higher susceptibility for endometriosis,MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 5 2008Yao-Yuan Hsieh Abstract DNA repair systems act to maintain genome integrity in the face of replication errors, environmental insults, and the cumulative effects of age. Genetic variants in DNA repair genes such as X-ray repair cross-complementing group 4 (XRCC4) might influence the ability to repair damaged DNA. Herein we aimed to investigate whether some XRCC4-related polymorphisms were associated with endometriosis susceptibility. Women were divided: (1) severe endometriosis (rAFS stage IV, n,=,136) and (2) nonendometriosis groups (n,=,112). The polymorphisms of XRCC4 codon 247, XRCC4 promoter ,1394, and XRCC4 intron 3 insertion/deletion (I/D) polymorphism were amplified by PCR and detected by electrophoresis after restriction enzyme (BBS I, Hinc II) digestions. Genotypes and allelic frequencies in both groups were compared. We observed that XRCC4 codon 247*A and XRCC4 promoter ,1394*T related genotypes, but not XRCC4 intron 3 I/D polymorphism, are associated with higher susceptibility for endometriosis. Distributions of XRCC4 codon 247*C homozygote/heterozygote/A homozygote, and C/A allele in both groups were: (1) 89/9.5/1.5% and 93.7/6.3%; (2) 97.3/2.7/0%, and 98.7/1.3% (P,<,0.05). Proportions of XRCC4 promoter ,1394*T homozygote/heterozygote/G homozygote and T/G allele in both groups were: (1) 94.1/5.2/0.7% and 96.7/3.3%, and (2) 79.4/17.9/2.7% and 88.4/11.6% (P,<,0.005). Proportions of XRCC4*I homozygote/heterozygote/D homozygote and A/C allele in both groups were: (1) 67.6/30.9/1.5% and 83.2/16.8%, and (2) 70.5/24.1/5.4% and 82.6/17.4% (nondifference). We conclude that XRCC4 codon 247*A and XRCC4 promoter ,1394*T related genotypes and alleles, but not XRCC4 intron 3 I/D polymorphism, might be associated with endometriosis susceptibilities and pathogenesis. Mol. Reprod. Dev. 75: 946,951, 2008. © 2008 Wiley-Liss, Inc. [source] DNA repair dysfunction in gastrointestinal tract cancersCANCER SCIENCE, Issue 3 2008Yoshihiko Maehara The DNA repair system surveys the genome, which is always suffering from exposure to both exogenous as well as endogenous mutagens, to maintain the genetic information. The fact that the basis of this DNA repair system is highly conserved, from prokaryote to mammalian cells, suggests the importance of precise genome maintenance mechanisms for organisms. In the past 15 years, considerable progress has been made in understanding how repair processes interact and how disruptions of these mechanisms lead to the accumulation of mutations and carcinogenesis. In 1993, two groups reported that DNA mismatch repair could be associated with hereditary non-polyposis colorectal cancer, indicating a connection between faulty DNA repair function and cancer. More recently, an inherited disorder of DNA glycosylase, which removes mutagenic oxidized base from DNA, has been reported in individuals with a predisposition to multiple colorectal adenomas and carcinomas. This is the first report that directly indicates the role of the repair of oxidative DNA in human inherited cancer. Studies from gene knockout mice have elucidated the principal role of these repair systems in the process of carcinogenesis. Moreover, clinical samples derived from cancer patients have shown the direct involvement. This review focuses on the function of DNA mismatch repair and oxidative DNA/nucleotide repair among various DNA repair systems in cells, both of which are essentially involved in the carcinogenesis of gastrointestinal tract cancer. (Cancer Sci 2008; 99: 451,458) [source] | ||||||||||