Document Detail


Translesion synthesis of 7,8-dihydro-8-oxo-2'-deoxyguanosine by DNA polymerase eta in vivo.
MedLine Citation:
PMID:  18359049     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
7,8-Dihydro-8-oxo-2'-deoxyguanosine (8-oxo-dG) is one of the most common DNA lesions induced by oxidative stress. This lesion can be bypassed by DNA polymerase eta (Pol eta) using in vitro translesion synthesis (TLS) reactions. However, the role that Pol eta plays in vivo contributing to 8-oxo-dG mutagenesis remains unclear. To clarify the role of Pol eta in 8-oxo-dG mutagenesis, we have used an siRNA knockdown approach in combination with a supF shuttle vector (pSP189) which replicates in mammalian cells. The pSP189 plasmid was treated with methylene blue plus light (MBL), which produces predominantly 8-oxo-dG in DNA, and was then replicated in GM637 cells in presence of siRNA that knocks down the expression of Pol eta, or in XP-V cells, which lack functional Pol eta. The mutant frequencies were increased in the Pol eta siRNA knockdown cells and in XP-V cells relative to control, meaning that Pol eta plays an important role in preventing 8-oxo-dG mutagenesis. In the same system, knockdown of OGG1 also led to an increase in mutagenesis. Neither the type of mutations nor their distribution along the supF gene were significantly different between control and target specific siRNA-transfected cells (or XP-V cells) and were predominantly G to T transversions. These results show that Pol eta has an important role in error-free 8-oxo-dG lesion bypass and avoidance of oxidative stress-induced mutagenesis in vivo.
Authors:
Dong-Hyun Lee; Gerd P Pfeifer
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-02-15
Journal Detail:
Title:  Mutation research     Volume:  641     ISSN:  0027-5107     ISO Abbreviation:  Mutat. Res.     Publication Date:  2008 May 
Date Detail:
Created Date:  2008-04-29     Completed Date:  2008-07-08     Revised Date:  2013-06-05    
Medline Journal Info:
Nlm Unique ID:  0400763     Medline TA:  Mutat Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  19-26     Citation Subset:  IM    
Affiliation:
Division of Biology, Beckman Research Institute of the City of Hope, Duarte, CA 91010, United States.
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MeSH Terms
Descriptor/Qualifier:
Base Sequence
Blotting, Western
Cells, Cultured
DNA / chemistry,  genetics*
DNA Damage*
DNA Glycosylases / genetics,  metabolism
DNA Repair
DNA Replication
DNA-Directed DNA Polymerase / antagonists & inhibitors,  genetics*
Deoxyguanosine / analogs & derivatives*,  genetics,  metabolism
Escherichia coli / genetics
Escherichia coli Proteins / metabolism
Fibroblasts / cytology,  metabolism
Genetic Vectors
Humans
Light
Methylene Blue / administration & dosage
Molecular Sequence Data
Mutagenesis*
RNA, Small Interfering / pharmacology
Skin / cytology,  metabolism
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Transfection
Xeroderma Pigmentosum / genetics
Grant Support
ID/Acronym/Agency:
ES06070/ES/NIEHS NIH HHS; R37 ES006070-16/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Escherichia coli Proteins; 0/RNA, Small Interfering; 61-73-4/Methylene Blue; 88847-89-6/8-oxo-7-hydrodeoxyguanosine; 9007-49-2/DNA; 961-07-9/Deoxyguanosine; EC 2.7.7.7/DNA-Directed DNA Polymerase; EC 2.7.7.7/Rad30 protein; EC 3.2.2.-/DNA Glycosylases; EC 3.2.2.-/oxoguanine glycosylase 1, human
Comments/Corrections

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