MOF and Histone H4 Acetylation at Lysine 16 Are Critical for DNA Damage Response and Double-Strand Break Repair

• DOI: 10.1128/mcb.01476-09
• Publication Date: 2010-05-18T03:25:51Z
• Authors: Girdhar G. Sharma; Sairei So; Arun Gupta; Rakesh Kumar; Christelle Cayrou; Nikita Avvakumov; Utpal Bhadra; Raj K. Pandita; Matthew H. Porteus; David J. Chen; Jacques Cote; Tej K. Pandita
• Keywords: Histone H4; DNA-PKcs; Non-homologous end joining; Ku80; Histone code

The human MOF gene encodes a protein that specifically acetylates histone H4 at lysine 16 (H4K16ac). Here we show reduced levels of H4K16ac correlate with defective DNA damage response (DDR) and double-strand break (DSB) repair to ionizing radiation (IR). defect, however, is not due altered expression proteins involved in DDR. Abrogation IR-induced DDR by depletion inhibited blocking deacetylation. was found be associated the DNA-dependent kinase catalytic subunit (DNA-PKcs), nonhomologous end-joining (NHEJ) repair. ATM-dependent phosphorylation DNA-PKcs also abrogated MOF-depleted cells. Our data indicate greatly decreased both NHEJ homologous recombination (HR). In addition, activity general chromatin upon colocalized synaptonemal complex male meiocytes. We propose MOF, through (histone code), has critical role multiple stages cellular DSB