scholarly journals The Effects of 1‐Nitropyrene on Oxidative DNA Damage and Expression of DNA Repair Enzymes

2005 ◽  
Vol 47 (3) ◽  
pp. 261-266 ◽  
Author(s):  
Yong‐Dae Kim ◽  
Young‐Jun Ko ◽  
Toshihiro Kawamoto ◽  
Heon Kim
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Oxidative Dna Damage ◽  
Dna Repair Enzymes ◽  
Repair Enzymes

scholarly journals Elevated Levels of Oxidative DNA Damage and DNA Repair Enzymes in Human Atherosclerotic Plaques

Circulation ◽  
2002 ◽  
Vol 106 (8) ◽  
pp. 927-932 ◽  
Author(s):  
Wim Martinet ◽  
Michiel W.M. Knaapen ◽  
Guido R.Y. De Meyer ◽  
Arnold G. Herman ◽  
Mark M. Kockx
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Oxidative Dna Damage ◽  
Atherosclerotic Plaques ◽  
Dna Repair Enzymes ◽  
Repair Enzymes

scholarly journals DNA damage shifts circadian clock time via Hausp-dependent Cry1 stabilization

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Stephanie J Papp ◽  
Anne-Laure Huber ◽  
Sabine D Jordan ◽  
Anna Kriebs ◽  
Madelena Nguyen ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Circadian Clock ◽  
Transcriptional Response ◽  
Genotoxic Stress ◽  
Genomic Integrity ◽  
Clock Time ◽  
Dna Repair Enzymes ◽  
Repair Enzymes ◽  
Specific Protease

The circadian transcriptional repressors cryptochrome 1 (Cry1) and 2 (Cry2) evolved from photolyases, bacterial light-activated DNA repair enzymes. In this study, we report that while they have lost DNA repair activity, Cry1/2 adapted to protect genomic integrity by responding to DNA damage through posttranslational modification and coordinating the downstream transcriptional response. We demonstrate that genotoxic stress stimulates Cry1 phosphorylation and its deubiquitination by Herpes virus associated ubiquitin-specific protease (Hausp, a.k.a Usp7), stabilizing Cry1 and shifting circadian clock time. DNA damage also increases Cry2 interaction with Fbxl3, destabilizing Cry2. Thus, genotoxic stress increases the Cry1/Cry2 ratio, suggesting distinct functions for Cry1 and Cry2 following DNA damage. Indeed, the transcriptional response to genotoxic stress is enhanced in Cry1−/− and blunted in Cry2−/− cells. Furthermore, Cry2−/− cells accumulate damaged DNA. These results suggest that Cry1 and Cry2, which evolved from DNA repair enzymes, protect genomic integrity via coordinated transcriptional regulation.

DNA Repair Gene Expression in CD34+ Bone Marrow Cells in MDS Patients with Mutiple Chromosomal Abnormalities by Array-Based Comparative Genomic Hybridization (A-CGH).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3423-3423
Author(s):  
Lukasz P. Gondek ◽  
Christine L. O’Keefe ◽  
Matt Kalaycio ◽  
Anjali Advani ◽  
Mikkael M. Sekeres ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Damage ◽  
Dna Repair ◽  
Cumulative Exposure ◽  
Dna Repair Genes ◽  
Dna Repair Enzymes ◽  
Chromosomal Structure ◽  
Repair Enzymes ◽  
Cd34 Cells ◽  
Repair Genes

Abstract Based on the high rate of chromosomal defects in MDS, inherent chromosomal instability (CIN) has been hypothesized as a key pathophysiologic factor of clonal evolution. Predisposition to DNA damage may be primarily due to acquired/inherited weakness in DNA repair machinery; such insufficiency may become manifest after a long latency following cumulative exposure to genotoxic agents. Subsequent changes in chromosomal structure and stepwise acquisition of neoplastic features could lead to leukemic progression. Previously, a number of allelic polymorphisms in DNA repair genes were observed. These variants may lead to altered expression of corresponding proteins. Conversely, if DNA damage is a primary defect, upregulation of specific DNA repair enzymes may be compensatory. Irrespective of the initial pathogenetic defect, we theorized that broad analysis of DNA repair machinery in MDS may point towards specific lesions that could be a subject of more targeted studies. Therefore, we examined levels of DNA repair enzymes using gene expression arrays. For proper comparisons, CD34 cells from 10 MDS patients (4 RA, 6 RAEB/RAEBt) and healthy controls were used. Expression array results were confirmed by Taqman PCR. Reference expression was established by pooling RNA from 12 controls. For more targeted analysis, A-CGH based genomic scan was used to better assess the extent of DNA damage in patients. The expression of 22 out of 113 DNA repair genes tested was detectable at levels >1,5X background; 2-level normalization of gene expression was performed according to variation of mRNA input (housekeeping gene-ACTB) and inter-assay variation in the signal intensity (biotinylated artificial sequence -BAS2C). Our combined standard sample was validated against individual controls; signals <1,5X pooled expression were obtained. Using expression levels of normal CD34 cells as a reference we found that 19 genes were upregulated in concordant fashion. The most dramatically increased genes included APEX, ATM, XRCC1, XRCC5 and MPG. This finding favors the theory that overexpression of the DNA repair machinery is a compensatory event to cope with a primarily increased level of DNA damage. When we subgrouped MDS patients according to FAB criteria, the expression of DNA repair genes (e.g., CIB1, ERCC1, SUMO1) increased with the malignant progression. For further analysis we have defined CIN phenotype by the presence of large or multiple small defects as determined by A-CGH. When patients with CIN vs. those with normal karyotype were compared, we found that chromosomal damage was not accompanied by a higher expression of DNA repair genes. MPG was most dramatically upregulated in all MDS patients. This gene involved in excision of methylated bases can induce single stranded breaks (SSB) and increase sensitivity to alkylating agents. Our finding suggest that either increased purine methylation induces a compensatory mechanism (MPG upregulation) or that overactivity of MPG itself results in increased base excision. Alternatively, overexpression of MPG may lead to SSB especially because downstream genes (e.g. XRCC3 or DNA ligase III) were not accordingly upregulated. In conclusion, our studies form a basis for further analysis of clinical phenotypes associated with upregulation of specific DNA repair genes and may indicate possible therapeutic targets in molecularly defined subtypes of MDS.

The influence of food constituents and genetic polymorphism of XME and DNA repair enzymes on DNA damage (DIEPHY study project)

2006 ◽  
Vol 164 ◽  
pp. S264
Author(s):  
J. Gromadzinska ◽  
J. Palus ◽  
G. Prochazka ◽  
D. Segerback ◽  
A. Seidel ◽  
...  
Keyword(s):  
Dna Damage ◽  
Dna Repair ◽  
Genetic Polymorphism ◽  
Dna Repair Enzymes ◽  
Repair Enzymes ◽  
Influence Of Food
Sign in / Sign up

Export Citation Format

Share Document