Document Detail

Extent of constitutive histone H2AX phosphorylation on Ser-139 varies in cells with different TP53 status.
MedLine Citation:
PMID:  16872365     Owner:  NLM     Status:  MEDLINE    
In response to DNA damage by genotoxic agents, histone H2AX is phosphorylated on Ser-139. However, during the cell cycle, predominantly in S and G(2)M phase, histone H2AX is also phosphorylated in untreated normal and tumour cells. This constitutive H2AX phosphorylation is markedly reduced by exposure of cells to the reactive oxygen species scavenger N-acetyl-L-cysteine. Therefore, it appears likely that constitutive H2AX phosphorylation reflects the ongoing oxidative DNA damage induced by the reactive oxygen species during progression through the cell cycle. Because the tumour suppressor p53 (tumour protein p53) is known to induce transcription of genes associated with cell response to oxidative stress, we have compared the intensity of constitutive H2AX phosphorylation, and the effect of N-acetyl-L-cysteine on it, in cells with different tumour protein p53 status. These were human lymphoblastoid cell lines derived from WIL2 cells: TK6, a p53 wt line, NH32, a tumour protein p53 knock-out derived from TK6, and WTK1, a WIL2-derived line that expresses a homozygous mutant of tumour protein p53. Also tested were the tumour protein p53-null promyelocytic HL-60 cells. The degree of constitutive H2AX phosphorylation was distinctly lower in NH32, WTK1 and HL-60 compared to TK6 cells in all phases of the cell cycle. Also, the degree of attenuation of constitutive H2AX phosphorylation by N-acetyl-L-cysteine was less pronounced in NH32, WTK1, and HL-60, compared to TK6 cells. However, the level of reactive oxygen species detected by the cells' ability to oxidize carboxyl-dichlorodihydrofluorescein diacetate was not significantly different in the cell lines studied, which would suggest that regardless of tumour protein p53 status, the level of oxidative DNA damage was similar. The observed higher level of constitutive H2AX phosphorylation in cells harbouring wt tumour protein p53 may thus indicate that tumour protein p53 plays a role in facilitating histone H2AX phosphorylation, an important step in the mobilization of the DNA repair machinery at the site of DNA double-strand breaks.
T Tanaka; A Kurose; X Huang; F Traganos; W Dai; Z Darzynkiewicz
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Cell proliferation     Volume:  39     ISSN:  0960-7722     ISO Abbreviation:  Cell Prolif.     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-07-28     Completed Date:  2006-09-11     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  9105195     Medline TA:  Cell Prolif     Country:  England    
Other Details:
Languages:  eng     Pagination:  313-23     Citation Subset:  IM    
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MeSH Terms
Acetylcysteine / pharmacology
Cell Cycle
Cell Line, Tumor
DNA Damage
DNA Repair
Fluorescent Dyes
Free Radical Scavengers / pharmacology
Histones / physiology*
Reactive Oxygen Species / metabolism
Serine / metabolism*
Tumor Suppressor Protein p53 / physiology*
Grant Support
R01 28 704//PHS HHS; R01 CA028704/CA/NCI NIH HHS; R01 CA028704-27/CA/NCI NIH HHS
Reg. No./Substance:
0/Fluorescent Dyes; 0/Free Radical Scavengers; 0/H2AFX protein, human; 0/Histones; 0/Reactive Oxygen Species; 0/Tumor Suppressor Protein p53; 452VLY9402/Serine; WYQ7N0BPYC/Acetylcysteine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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