Tissue-specific DNA-PK-dependent H2AX phosphorylation and {gamma}-H2AX elimination after X-irradiation in vivo

Journal Article · Fri Nov 07 04:00:00 EST 2008 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2008.08.095· OSTI ID:21146675

Koike, Manabu ^[1]; Sugasawa, Jun; Yasuda, Mariko; Koike, Aki ^[1]

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1. DNA Repair Gene Research, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba 263-8555 (Japan)

Histone H2AX rapidly undergoes phosphorylation at Ser139 ({gamma}-H2AX) in response to DNA double-strand breaks. Although ATM kinase and DNA-PK phosphorylate Ser139 of H2AX in culture cells, the regulatory mechanism of {gamma}-H2AX level remains unclear in vivo. Here, we detected the phosphorylation of H2AX and the elimination of {gamma}-H2AX in the mouse skin after X-irradiation. Furthermore, following X-irradiation, the level of {gamma}-H2AX also increased in mice lacking either ATM or DNA-PK. Although the elimination after X-irradiation was detected in the skin of these mutant mice, the elimination in DNA-PK-deficient mice was slower than that in C3H and ATM knockout mice, suggesting that a fraction of {gamma}-H2AX in the skin is eliminated in a DNA-PK-dependent manner. Although the DNA-PK-dependent elimination of {gamma}-H2AX was also detected in the liver, kidney, and spleen, the DNA-PK-dependent phosphorylation of H2AX was detected in the spleen only. These results suggest that the regulatory mechanism of {gamma}-H2AX level is tissue-specific.

• OSTI ID: 21146675
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 376; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
CELL CULTURES
CHEMILUMINESCENCE
DNA
IN VIVO
IONIZING RADIATIONS
IRRADIATION
KIDNEYS
KNOCK-OUT REACTIONS
LIVER
MICE
PHOSPHORYLATION
SKIN
SPLEEN
STRAND BREAKS