Acetylated lysine 56 on histone H3 drives chromatin assembly after repair, signaling for the completion of repair

• Published in: Cell Vol. 134; no. 2; pp. 231 - 243
• Main Authors: Chen, Chin-Chuan, Carson, Joshua J., Feser, Jason, Tamburini, Beth, Zabaronick, Susan, Linger, Jeffrey, Tyler, Jessica K.
• Format: Journal Article
• Language: English
• Published: 25.07.2008
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2008.06.035

The mechanisms whereby chromatin structure and cell cycle progression are restored after DNA repair are largely unknown. We show that chromatin is reassembled following double-strand break (DSB) repair and that this requires the histone chaperone Asf1. Absence of Asf1 causes persistent activation of the DNA damage checkpoint after DSB repair as a consequence of defective checkpoint recovery, leading to cell death. The contribution of Asf1 towards chromatin assembly after DSB repair is due to its role in promoting acetylation of free histone H3 on lysine 56 (K56) by the histone acetyl transferase Rtt109, because mimicking acetylation of K56 bypasses the requirement for Asf1 for chromatin reassembly and checkpoint recovery after repair, while mutations that prevent K56 acetylation block chromatin reassembly after repair. These results indicate that restoration of the chromatin following DSB repair is driven by acetylated H3 K56 and that this is a signal for the completion of repair.