title: Large-scale heterochromatin remodeling linked to overreplication-associated DNA damage.
abstract: Previously, we have shown that loss of the histone 3 lysine 27 (H3K27) monomethyltransferases ARABIDOPSIS TRITHORAX-RELATED 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.
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405.
authors.forename: Wei
authors.initials: W
authors.lastname: Feng
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hale
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405.
authors.forename: Ryan S
authors.initials: RS
authors.lastname: Over
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095.
authors.forename: Shawn J
authors.initials: SJ
authors.lastname: Cokus
authors.affiliation: Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095; michaels@indiana.edu jacobsen@ucla.edu.|Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Jacobsen
authors.affiliation: Department of Biology, Indiana University, Bloomington, IN 47405; michaels@indiana.edu jacobsen@ucla.edu.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Michaels
mesh_terms: D017360:Arabidopsis / Q000235:genetics; D029681:Arabidopsis Proteins / Q000235:genetics; D002843:Chromatin / Q000235:genetics; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics; D018506:Gene Expression Regulation, Plant / Q000235:genetics; D006570:Heterochromatin / Q000235:genetics*; D006657:Histones / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000235:genetics
chemical_list: D029681:Arabidopsis Proteins; D002843:Chromatin; D006570:Heterochromatin; D006657:Histones; C542364:ATXR5 protein, Arabidopsis; C542365:ATXR6 protein, Arabidopsis; D008780:Methyltransferases
keywords: ATXR5; ATXR6; DNA repair; DNA replication; H3K27me1