Genomic instability and endoreduplication triggered by RAD17 deletion
- 1Departments of Experimental Radiation Oncology, 4Epidemiology, and 6Molecular Genetics, University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030; 2Verna & Mars McLean Department of Biochemistry and Molecular Biology, 3Howard Hughes Medical Institute, and 5Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA
Abstract
Cell cycle checkpoints are critical for genomic stability. Rad17, a component of the checkpoint clamp loader complex (Rad17/Rfc2-5), is required for the response to DNA damage and replication stress. To explore the role of Rad17 in the maintenance of genomic integrity, we established somatic conditional alleles of RAD17 in human cells. We find that RAD17 is not only important for the Atr-mediated checkpoint but is also essential for cell viability. Cells lacking RAD17 exhibited acute chromosomal aberrations and underwent endoreduplication at a high rate. Therefore, RAD17links the checkpoint to ploidy control and is essential for the maintenance of chromosomal stability.
Keywords
Footnotes
-
↵7 Corresponding author.
-
E-MAIL leili{at}mdanderson.org; FAX (713) 794-5369.
-
Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1065103.
-
- Received December 6, 2002.
- Accepted February 19, 2003.
- Cold Spring Harbor Laboratory Press
