Document Detail


DNA damage signaling assessed in individual cells in relation to the cell cycle phase and induction of apoptosis.
MedLine Citation:
PMID:  23137030     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Reviewed are the phosphorylation events reporting activation of protein kinases and the key substrates critical for the DNA damage signaling (DDS). These DDS events are detected immunocytochemically using phospho-specific Abs; flow cytometry or image-assisted cytometry provide the means to quantitatively assess them on a cell by cell basis. The multiparameter analysis of the data is used to correlate these events with each other and relate to the cell cycle phase, DNA replication and induction of apoptosis. Expression of γH2AX as a possible marker of induction of DNA double strand breaks is the most widely studied event of DDS. Reviewed are applications of this multiparameter approach to investigate constitutive DDS reporting DNA damage by endogenous oxidants byproducts of oxidative phosphorylation. Also reviewed are its applications to detect and explore mechanisms of DDS induced by variety of exogenous agents targeting DNA such as exogenous oxidants, ionizing radiation, radiomimetic drugs, UV light, DNA topoisomerase I and II inhibitors, DNA crosslinking drugs and variety of environmental genotoxins. Analysis of DDS induced by these agents provides often a wealth of information about mechanism of induction and the type of DNA damage (lesion) and is reviewed in the context of cell cycle phase specificity, DNA replication, and induction of apoptosis or cell senescence. Critically assessed is interpretation of the data as to whether the observed DDS events report induction of a particular type of DNA lesion.
Authors:
Zbigniew Darzynkiewicz; Hong Zhao; H Dorota Halicka; Paulina Rybak; Jurek Dobrucki; Donald Wlodkowic
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review     Date:  2012-11-09
Journal Detail:
Title:  Critical reviews in clinical laboratory sciences     Volume:  49     ISSN:  1549-781X     ISO Abbreviation:  Crit Rev Clin Lab Sci     Publication Date:    2012 Sep-Dec
Date Detail:
Created Date:  2012-12-14     Completed Date:  2013-09-23     Revised Date:  2013-11-14    
Medline Journal Info:
Nlm Unique ID:  8914816     Medline TA:  Crit Rev Clin Lab Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  199-217     Citation Subset:  IM    
Affiliation:
Brander Cancer Research Institute and Department of Pathology, New York Medical College, Valhalla, NY 10595, USA. darzynk@nymc.edu
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MeSH Terms
Descriptor/Qualifier:
Apoptosis*
Cell Cycle*
Cells / metabolism*
DNA Damage*
Flow Cytometry
Humans
Signal Transduction*
Grant Support
ID/Acronym/Agency:
NCI RO1 28 704//PHS HHS; R01 CA028704/CA/NCI NIH HHS; //Biotechnology and Biological Sciences Research Council
Comments/Corrections

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