Localized histone acetylation and deacetylation triggered by the homologous recombination pathway of double-strand DNA repair.
Many recent studies have demonstrated recruitment of chromatin-modifying enzymes to double-strand breaks. Instead, we wanted to examine chromatin modifications during the repair of these double-strand breaks. We show that homologous recombination triggers the acetylation of N-terminal lysines on histones H3 and H4 flanking a double-strand break, followed by deacetylation of H3 and H4. Consistent with a requirement for acetylation and deacetylation during homologous recombination, Saccharomyces cerevisiae with substitutions of the acetylatable lysines of histone H4, deleted for the N-terminal tail of histone H3 or H4, deleted for the histone acetyltransferase GCN5 gene or the histone deacetylase RPD3 gene, shows inviability following induction of an HO lesion that is repaired primarily by homologous recombination. Furthermore, the histone acetyltransferases Gcn5 and Esa1 and the histone deacetylases Rpd3, Sir2, and Hst1 are recruited to the HO lesion during homologous recombinational repair. We have also observed a distinct pattern of histone deacetylation at the donor locus during homologous recombination. Our results demonstrate that dynamic changes in histone acetylation accompany homologous recombination and that the ability to modulate histone acetylation is essential for viability following homologous recombination.
Tamburini
Beth A
BA
Department of Biochemistry and Molecular Genetics, University of Colorado Health Sciences Center at Fitzsimons, P.O. Box 6511, Aurora, CO 80045, USA.
Tyler
Jessica K
JK
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism*; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D056565:Sirtuin 2; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D004247:DNA; D004268:DNA-Binding Proteins; D015252:Deoxyribonucleases, Type II Site-Specific; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases; D006657:Histones; D008239:Lysine; D011494:Protein Kinases; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae; D056565:Sirtuin 2; D037761:Sirtuins; D014157:Transcription Factors; C496551:Esa1 protein, S cerevisiae; C501392:GCN5 protein, S cerevisiae; D000099224:p300-CBP-Associated Factor; C530845:HO protein, S cerevisiae; C037725:SCEI protein, S cerevisiae; C103934:HST1 protein, S cerevisiae; C071665:RPD3 protein, S cerevisiae; C087778:SIR2 protein, S cerevisiae