title: Genomic instability and endoreduplication triggered by RAD17 deletion.
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, RAD17 links the checkpoint to ploidy control and is essential for the maintenance of chromosomal stability.
authors.affiliation: Department of Experimental Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.forename: Lee
authors.initials: L
authors.lastname: Zou
authors.forename: Huyong
authors.initials: H
authors.lastname: Zheng
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
authors.forename: Lei
authors.initials: L
authors.lastname: Li
mesh_terms: D015139:Blotting, Southern; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000502:physiology*; D002470:Cell Survival; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D003106:Colon / Q000473:pathology; D004249:DNA Damage; D004847:Epithelial Cells / Q000473:pathology; D005090:Exodeoxyribonucleases; D017353:Gene Deletion; D020440:Gene Duplication; D006801:Humans; D019426:Integrases / Q000378:metabolism; D007621:Karyotyping; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D014162:Transfection; D014764:Viral Proteins / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D010750:Phosphoproteins; C113575:Rad17 protein, human; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1