title: A YY1-INO80 complex regulates genomic stability through homologous recombination-based repair.
abstract: DNA damage repair is crucial for the maintenance of genome integrity and cancer suppression. We found that loss of the mouse transcription factor YY1 resulted in polyploidy and chromatid aberrations, which are signatures of defects in homologous recombination. Further biochemical analyses identified a YY1 complex comprising components of the evolutionarily conserved INO80 chromatin-remodeling complex. Notably, RNA interference-mediated knockdown of YY1 and INO80 increased cellular sensitivity toward DNA-damaging agents. Functional assays revealed that both YY1 and INO80 are essential in homologous recombination-based DNA repair (HRR), which was further supported by the finding that YY1 preferentially bound a recombination-intermediate structure in vitro. Collectively, these observations reveal a link between YY1 and INO80 and roles for both in HRR, providing new insight into mechanisms that control the cellular response to genotoxic stress.
authors.affiliation: Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Su
authors.initials: S
authors.lastname: Wu
authors.forename: Yujiang
authors.initials: Y
authors.lastname: Shi
authors.forename: Peter
authors.initials: P
authors.lastname: Mulligan
authors.forename: Frédérique
authors.initials: F
authors.lastname: Gay
authors.forename: Joseph
authors.initials: J
authors.lastname: Landry
authors.forename: Huifei
authors.initials: H
authors.lastname: Liu
authors.forename: Ju
authors.initials: J
authors.lastname: Lu
authors.forename: Hank H
authors.initials: HH
authors.lastname: Qi
authors.forename: Weijia
authors.initials: W
authors.lastname: Wang
authors.forename: Jac A
authors.initials: JA
authors.lastname: Nickoloff
authors.forename: Carl
authors.initials: C
authors.lastname: Wu
authors.forename: Yang
authors.initials: Y
authors.lastname: Shi
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D004249:DNA Damage; D004265:DNA Helicases / Q000502:physiology*; D004260:DNA Repair / Q000502:physiology*; D042822:Genomic Instability; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D011123:Polyploidy; D034622:RNA Interference; D011995:Recombination, Genetic; D050986:YY1 Transcription Factor / Q000502:physiology*
chemical_list: D050986:YY1 Transcription Factor; C494699:Yy1 protein, mouse; D004265:DNA Helicases