Journal
JOURNAL OF CELL BIOLOGY
Volume 160, Issue 7, Pages 1017-1027Publisher
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200209065
Keywords
HDAC4; 53BP1; DNA damage; irradiation; G2 checkpoint
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Funding
- NCI NIH HHS [P01-CA75138-05, P30 CA006927, P01 CA06927, P01 CA075138] Funding Source: Medline
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A number of proteins are recruited to nuclear foci upon exposure to double-strand DNA damage, including 53BP1 and Rad51, but the precise role of these DNA damage-induced foci remain unclear. Here we show in a variety of human cell lines that histone deacetylase (HDAC) 4 is recruited to foci with kinetics similar to, and colocalizes with, 53BP1 after exposure to agents causing double-stranded DNA breaks. HDAC4 foci gradually disappeared in repair-proficient cells but persisted in repair-deficient cell lines or cells irradiated with a lethal dose, suggesting that resolution of HDAC4 foci is linked to repair. Silencing of HDAC4 via RNA interference surprisingly also decreased levels of 53BP1 protein, abrogated the DNA damage-induced G2 delay, and radiosensitized HeLa cells. Our combined results suggest that HDAC4 is a critical component of the DNA damage response pathway that acts through 53BP1 and perhaps contributes in maintaining the G2 cell cycle checkpoint.
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