Large-scale heterochromatin remodeling linked to overreplication-associated DNA damage

作者：Feng Wei; Hale Christopher J; Over Ryan S; Cokus Shawn J; Jacobsen Steven E^*; Michaels Scott D^*

来源：Proceedings of the National Academy of Sciences of the United States of America, 2017, 114(2): 406-411.

DOI：10.1073/pnas.1619774114

• ATXR5
• ATXR6
• H3K27me1
• DNA repair
• DNA replication

Previously, we have shown that loss of the histone 3 lysine 27 (H3K27) monomethyltransferases ARABIDOPSIS TRITHORAXRELATED 5 (ATXR5) and ATXR6 (ATXR6) results in the overreplication of heterochromatin. Here we show that the overreplication results in DNA damage and extensive chromocenter remodeling into unique structures we have named "overreplication-associated centers" (RACs). RACs have a highly ordered structure with an outer layer of condensed heterochromatin, an inner layer enriched in the histone variant H2AX, and a low-density core containing foci of phosphorylated H2AX (a marker of double-strand breaks) and the DNA-repair enzyme RAD51. atxr5,6 mutants are strongly affected by mutations in DNA repair, such as ATM and ATR. Because of its dense packaging and repetitive DNA sequence, heterochromatin is a challenging environment in which to repair DNA damage. Previous work in animals has shown that heterochromatic breaks are translocated out of the heterochromatic domain for repair. Our results show that atxr5,6 mutants use a variation on this strategy for repairing heterochromatic DNA damage. Rather than being moved to adjacent euchromatic regions, as in animals, heterochromatin undergoes large-scale remodeling to create a compartment with low chromatin density.

• 出版日期2017-1-10