title: Double-strand breaks in heterochromatin move outside of a dynamic HP1a domain to complete recombinational repair.
abstract: Double-strand breaks (DSBs) in heterochromatic repetitive DNAs pose significant threats to genome integrity, but information about how such lesions are processed and repaired is sparse. We observe dramatic expansion and dynamic protrusions of the heterochromatin domain in response to ionizing radiation (IR) in Drosophila cells. We also find that heterochromatic DSBs are repaired by homologous recombination (HR) but with striking differences from euchromatin. Proteins involved in early HR events (resection) are rapidly recruited to DSBs within heterochromatin. In contrast, Rad51, which mediates strand invasion, only associates with DSBs that relocalize outside of the domain. Heterochromatin expansion and relocalization of foci require checkpoint and resection proteins. Finally, the Smc5/6 complex is enriched in heterochromatin and is required to exclude Rad51 from the domain and prevent abnormal recombination. We propose that the spatial and temporal control of DSB repair in heterochromatin safeguards genome stability by preventing aberrant exchanges between repeats.
authors.affiliation: Department of Genome Dynamics, Lawrence Berkeley National Laboratory, Berkeley, CA 94720, USA.
authors.forename: Irene
authors.initials: I
authors.lastname: Chiolo
authors.forename: Aki
authors.initials: A
authors.lastname: Minoda
authors.forename: Serafin U
authors.initials: SU
authors.lastname: Colmenares
authors.forename: Aris
authors.initials: A
authors.lastname: Polyzos
authors.forename: Sylvain V
authors.initials: SV
authors.lastname: Costes
authors.forename: Gary H
authors.initials: GH
authors.lastname: Karpen
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism; D006570:Heterochromatin; D051135:Rad51 Recombinase / Q000378:metabolism; D011995:Recombination, Genetic
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D006570:Heterochromatin; C585451:SMC5 protein, Drosophila; C585452:jnj protein, Drosophila; D000090266:Chromobox Protein Homolog 5; D051135:Rad51 Recombinase