Human DNA repair systems: An overview

Yu, Zhe; Chen, Jian; Ford, Barry N.; Brackley, Moyra E.; Glickman, Barry W.

doi:10.1002/(sici)1098-2280(1999)33:1<3::aid-em2>3.0.co;2-l

Cited by 172 publications

(100 citation statements)

References 196 publications

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“…One molecular mechanism of gene inactivation of these DNA repair enzymes is promoter methylation of CpG islands. 33,34 In our analysis, we detected a loss of hMLH1 expression revealed by immunohistochemistry in 50% of multiple myeloma cases, whereas none of the monoclonal gammopathies of undetermined significance cases had a loss of expression of this repair enzyme. With the methylation-specific PCR technique, we also found that 10% of myeloma cases had hMLH1 promoter methylation.…”

Section: Discussionmentioning

confidence: 56%

hMLH1 and MGMT inactivation as a mechanism of tumorigenesis in monoclonal gammopathies

et al. 2006

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Monoclonal gammopathies are a group of disorders characterized by clonal proliferation and accumulation of immunoglobulin-producing plasma cells. Multiple myeloma and monoclonal gammopathy of undetermined significance are the most common monoclonal gammopathies; the two comprise a spectrum of disorders, ranging from a relatively benign disease, monoclonal gammopathy of undetermined significance, to a malignant disease, multiple myeloma. Aberrant promoter methylation represents a primary mechanism of gene silencing during tumorigenesis. DNA repair systems act to maintain genome integrity in the presence of replication errors, environmental insults, and the cumulative effects of aging. The methylation patterns of two genes implicated in DNA repair, O6 methylguanine DNA methyl-transferase (MGMT) and human mutL homologue1 (hMLH1) have been detected in various solid tumours. With the purpose of studying the gene silencing of MGMT and hMLH1 in plasma cell disorders, we investigated the methylation status and expression of both genes in: 29 cases of multiple myeloma; one case of plasma cell leukaemia; 13 cases of monoclonal gammopathy of undetermined significance; and two cases of polyclonal plasmacytosis, using methylationspecific polymerase-chain reaction and immunohistochemical techniques. Methylation frequencies for MGMT were 23% in multiple myeloma and 8% in monoclonal gammopathy of undetermined significance. It was 10% for hMLH1 in multiple myeloma. None of the patients diagnosed with monoclonal gammopathy of undetermined significance had hMLH1 hypermethylated. In addition, 50% of myeloma cases had a loss of hMLH1 expression, whereas silencing of MGMT was observed in 43% of myeloma and 36% of samples with monoclonal gammopathy of undetermined significance. This study indicates that repair pathway defects play a role in the pathogenesis and evolution of monoclonal gammopathies, and suggests that inactivation of hMLH1 could be implicated in multiple myeloma tumorigenesis.

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Section: Discussionmentioning

confidence: 56%

hMLH1 and MGMT inactivation as a mechanism of tumorigenesis in monoclonal gammopathies

et al. 2006

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“…The level of DNA damage repair capacity is an important factor affecting the radiosensitivity. For DNA damage repair, there are four major signaling pathways known: the base excision repair (BER), the nucleotide excision repair (NER), the mismatch repair (MMR), and the double strand break repair (DSBR) (Yu et al, 1999;Wood et al, 2001). The BER pathway and NER are important for the repair of damaged (Hoeijmakers, 2001).…”

Section: Discussionmentioning

confidence: 99%

DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

Guo

Yang²,

Pei³

et al. 2015

Asian Pacific Journal of Cancer Prevention

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Background: : A number of association studies have been carried out to investigate the relationship between genetic polymorphisms in DNA repair genes and response to radiotherapy-based multimodality treatment of patients with rectal cancer. However, their conclusions were inconsistent. The objective of the present study was to assess the role of DNA repair gene genetic polymorphisms in predicting genetic biomarkers of the response in rectal cancer patients treated with neoadjuvant chemoradiation. Materials and Methods: Studies were retrieved by searching the PubMed database, Cochrane Library, Embase, and ISI Web of Knowledge. We conducted a meta-analysis to evaluate the association between genetic polymorphisms and the response in rectal cancer treated with neoadjuvant chemoradiation by checking odds ratios (ORs) and 95% confidence intervals (CIs). Results: Data were extracted from 5 clinical studies for this meta-analysis. The results showed that XRCC1 RS25487, XRCC1 RS179978, XRCC3 RS861539, ERCC1 RS11615 and ERCC2 RS13181 were not associated with the response in the radiotherapy-based multimodality treatment of patients with rectal cancer (p>0.05). Conclusions: This study shows that DNA repair gene common genetic polymorphisms are not significantly correlated with the radiotherapy-based multimodality treatment in rectal cancer patients.

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“…Apoptosis, a goal of cancer treatment, is characterized by the cell shrinkage, blebbing of the plasma membrane, and chromatin condensation that are associated with cleavage of DNA into ladders [20,21]. However, in response to some effective therapeutic treatments, decreased ability to undergo apoptosis occurred in human malignant tumor cells [22,23].…”

Section: Introductionmentioning

confidence: 99%

Role of p53, PUMA, and Bax in wogonin-induced apoptosis in human cancer cells

Lee

Kim

Zhang

et al. 2008

Biochemical Pharmacology

120

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We observed that treatment of prostate cancer cells for 24 h with wogonin, a naturally occurring monoflavonoid, induced cell death in a dose-and time-dependent manner. Exposure of wogonin to LNCaP cells was associated with increased intracellular levels of p21 Cip-1 , p27 Kip-1 , p53, and PUMA, oligomerization of Bax, release of cytochrome c from the mitochondria, and activation of caspases. We also confirmed the role of p53 by noting that knock-in in p53 expression by transfecting p53 DNA increased wogonin-induced apoptosis in p53-null PC-3 cells. To study the mechanism of PUMA upregulation, we determined the activities of PUMA promoter in the wogonin treated and untreated cells. Increase of the intracellular levels of PUMA protein was due to increase in transcriptional activity. Data from chromatin immunoprecipitation (ChIP) analyses revealed that wogonin activated the transcription factor p53 binding activity to the PUMA promoter region. We observed that the upregulation of PUMA mediated wogonin cytotoxicity. Further characterization of the transcriptional response to wogonin in HCT116 human colon cancer cells demonstrated that PUMA induction was p53-dependent; deficiency in either p53 or PUMA significantly protected HCT116 cells against wogonin-induced apoptosis. Also, wogonin promoted mitochondrial translocation and multimerization of Bax. Interestingly, wogonin (100 μM) treatment did not affect the viability of normal human prostate epithelial cells (PrEC). Taken together, these results indicate that p53-dependent transcriptional induction of PUMA and oligomerization of Bax play important roles in the sensitivity of cancer cells to apoptosis induced by caspase activation through wogonin.

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Human DNA repair systems: An overview

Cited by 172 publications

References 196 publications

hMLH1 and MGMT inactivation as a mechanism of tumorigenesis in monoclonal gammopathies

hMLH1 and MGMT inactivation as a mechanism of tumorigenesis in monoclonal gammopathies

DNA Repair Gene Polymorphisms Do Not Predict Response to Radiotherapy-Based Multimodality Treatment of Patients with Rectal Cancer: a Meta-analysis

Role of p53, PUMA, and Bax in wogonin-induced apoptosis in human cancer cells

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