Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response.

Journal article

Anumber 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.

Authors: Kao, G; McKenna, W; Guenther, MG; Muschel, R; Lazar, M

• Publication status: Published
• Journal: Journal of cell biology
• Volume: 160
• Issue: 7
• Pages: 1017-1027
• Publication date: 2003-03-01
• DOI: 10.1083/jcb.200209065
• EISSN: 1540-8140
• ISSN: 0021-9525
• Language: English
• Keywords: Gamma Rays; DNA Damage; Carrier Proteins; Phosphoproteins; Hydroxamic Acids; Kinetics; Etoposide; Repressor Proteins; Protein Synthesis Inhibitors; Humans; Cell Line; Nucleic Acid Synthesis Inhibitors; DNA-Binding Proteins; Nuclear Proteins; DNA Repair; G2 Phase; RNA, Small Interfering; Mutation; Cell Nucleus; Intracellular Signaling Peptides and Proteins; Tumor Cells, Cultured; Histone Deacetylases; Dose-Response Relationship, Radiation