Chromatin modifications in response to DNA double-strand breaks
DNA double-strand breaks (DSBs) are among the most toxic DNA lesions, and cells have to respond to DSBs quickly and in an efficient way in order to make sure that they are properly repaired. The response to DSBs involves modifications of the surrounding chromatin to generate dedicated repair domains. To mount these modifications in a robust and self-reinforcing manner, cells employ feed-forward mechanism. This provides a robust chromatin response beneficial for DSB repair, yet it comes with the risk that excessive spreading of DNA break-induced chromatin modifications may also affect undamaged areas of the genome. Indeed, we recently discovered that self-amplificatory chromatin transactions must be tightly controlled and actively restrained to remain locally and temporally confined, and one research focus of the lab lies on the cellular mechanisms that prevent excessive and potentially detrimental chromatin modifications in response to DNA breakage.
Further reading:
Rother & Pellegrino et al.
CHD7 and 53BP1 regulate distinct pathways for the re-ligation of DNA double-strand breaks
Nat Commun. 2020 Nov 13;11(1):5775.
Michelena et al.
Replicated chromatin curtails 53BP1 recruitment in BRCA1-proficient and BRCA1-deficient cells
Life Sci Alliance. 2021 Apr 2;4(6):e202101023.
Pellegrino et al.
Replication-Coupled Dilution of H4K20me2 Guides 53BP1 to Pre-replicative Chromatin
Cell Reports 19, 1819–1831, 2017
Pellegrino & Altmeyer
Interplay between Ubiquitin, SUMO, and Poly(ADP-Ribose) in the Cellular Response to Genotoxic Stress.
Front Genet. 2016 Apr 19;7:63.
Altmeyer & Lukas
Guarding against collateral damage during chromatin transactions
Cell 2013;153(7):1431-4