Article abstract
Nature Structural & Molecular Biology 14, 1165 - 1172 (2007)
Published online: 18 November 2007 | doi:10.1038/nsmb1332
A YY1–INO80 complex regulates genomic stability through homologous recombination–based repair
Su Wu1, Yujiang Shi1,5, Peter Mulligan1, Frédérique Gay1, Joseph Landry2, Huifei Liu1, Ju Lu3, Hank H Qi1, Weijia Wang1, Jac A Nickoloff4, Carl Wu2 & Yang Shi1
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.
- Department of Pathology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
- Laboratory of Biochemistry, National Cancer Institute, US National Institutes of Health, Building 37, Rood 4C-09, Bethesda, Maryland 20892-4255, USA.
- Program in Neuroscience, Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
- Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, 915 Camino de Salud NE, Albuquerque, New Mexico 87131, USA.
- Present address: Division of Endocrinology, Hypertension and Diabetes, Brigham and Women's Hospital, 221 Longwood Avenue, EBRC 222A, Boston, Massachusetts 02115, USA.
Correspondence to: Yang Shi1 e-mail: yang_shi@hms.harvard.edu
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cellsThe EMBO Journal Article (17 Nov 2003)
Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cellsThe EMBO Journal Article (17 Nov 2003)
Eme1 is involved in DNA damage processing and maintenance of genomic stability in mammalian cellsThe EMBO Journal Article (17 Nov 2003)
Replication blocking lesions present a unique substrate for homologous recombinationThe EMBO Journal Article
See all 14 matches for Research
