H3K9me3 and H4K20me3 represent the epigenetic landscape for 53BP1 binding to DNA lesions

0501862 - BFÚ 2019 RIV US eng J - Článek v odborném periodiku
Kovaříková, Alena - Legartová, Soňa - Krejčí, Jana - Bártová, Eva
H3K9me3 and H4K20me3 represent the epigenetic landscape for 53BP1 binding to DNA lesions.
Aging. Roč. 10, č. 10 (2018), s. 2585-2605. ISSN 1945-4589
Grant CEP: GA ČR(CZ) GA18-07384S
Grant ostatní: AV ČR(CZ) StrategieAV21/7
Program: StrategieAV
Institucionální podpora: RVO:68081707
Klíčová slova: double-strand breaks * histone H3 * cell-cycle * heterochromatin protein-1
Obor OECD: Cell biology
Impakt faktor: 5.515, rok: 2018

Methylation of histones H4 at lysine 20 position (H4K20me), which is functional in DNA repair, represents a binding site for the 53BP1 protein. Here, we show a radiation-induced increase in the level of H4K20me3 while the levels of H4K20me1 and H4K20me2 remained intact. H4K20me3 was significantly pronounced at DNA lesions in only the G1 phase of the cycle, while this histone mark was reduced in very late S and G2 phases when PCNA was recruited to locally micro-irradiated chromatin. H4K20me3 was diminished in locally irradiated Suv39h1/h2 double knockout (dn) fibroblasts, and the same phenomenon was observed for H3K9me3 and its binding partner, the HP1 beta protein. Immunoprecipitation showed the existence of an interaction between H3K9me3-53BP1 and H4K20me3-53BP1, however, HP1 beta did not interact with 53BP1. Together, H3K9me3 and H4K20me3 represent epigenetic markers that are important for the function of the 53BP1 protein in non-homologous end joining (NHEJ) repair. The very late S phase represents the cell cycle breakpoint when a DDR function of the H4K20me3-53BP1 complex is abrogated due to recruitment of the PCNA protein and other DNA repair factors of homologous recombination to DNA lesions.
Trvalý link: http://hdl.handle.net/11104/0293837