title: DNA damage in the presence of chemical genotoxic agents induce acetylation of H3K56 and H4K16 but not H3K9 in mammalian cells.
abstract: Histone covalent modifications play a significant role in the regulation of chromatin structure and function during DNA damage. Hyperacetylation of histones is a DNA damage dependent post translational modification in yeast and mammals. Although acetylation of histones during DNA damage is well established, specific lysine residues that are acetylated is being understood very recently in mammals. Here, in the present study, acetylation of three different lysine residues Histone3Lysine 9 (H3K9), Histone3Lysine 56 (H3K56) and Histone4Lysine 16 (H4K16) were probed with specific antibodies in mammalian cell lines treated with genotoxic agents that induce replication stress or S-phase dependent double strand breaks. Immunoblotting results have shown that DNA damage associated with replication arrest induce acetylation of H3K56 and H4K16 but not H3K9 in mammals. Immunofluorescence experiments further confirmed that acetylated H3K56 and H4K16 form nuclear foci at the site of DNA double strand breaks. Colocalization of H3K56ac with γ H2AX and replication factor PCNA proved the existence of this modification at the site of DNA damage and its probable role in DNA damage repair. Put together, the present data suggests that acetylation of H3K56 and H4K16 are potent DNA damage dependent histone modifications but not H3K9 in mammals.
authors.affiliation: Epigenetics and Cancer Biology Lab, Institute of Life Sciences, University of Hyderabad, Gachibowli, Hyderabad, 500 046, India. rahulvbio@gmail.com
authors.forename: Rahul Kumar
authors.initials: RK
authors.lastname: Vempati
authors.forename: Devyani
authors.initials: D
authors.lastname: Haldar
mesh_terms: D000107:Acetylation / Q000187:drug effects; D004249:DNA Damage / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D057809:HEK293 Cells; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008239:Lysine / Q000378:metabolism*; D009153:Mutagens / Q000633:toxicity*
chemical_list: D006657:Histones; D009153:Mutagens; D008239:Lysine