Genomic instability and endoreduplication triggered byRAD17deletion
Open Access
- 2 April 2003
- journal article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 17 (8), 965-970
- https://doi.org/10.1101/gad.1065103
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
This publication has 29 references indexed in Scilit:
- SMC1 is a downstream effector in the ATM/NBS1 branch of the human S-phase checkpointGenes & Development, 2002
- Involvement of the cohesin protein, Smc1, in Atm-dependent and independent responses to DNA damageGenes & Development, 2002
- Replication licensing — Origin licensing: defining the proliferative state?Trends in Cell Biology, 2002
- Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatinGenes & Development, 2002
- Structure-Function Analysis of Fission Yeast Hus1-Rad1-Rad9 Checkpoint ComplexMolecular Biology of the Cell, 2001
- ATR and ATRIP: Partners in Checkpoint SignalingScience, 2001
- Two checkpoint complexes are independently recruited to sites of DNA damage in vivoGenes & Development, 2001
- Recruitment of Mec1 and Ddc1 Checkpoint Proteins to Double-Strand Breaks Through Distinct MechanismsScience, 2001
- Purification and characterization of human DNA damage checkpoint Rad complexesProceedings of the National Academy of Sciences, 2001
- Cell cycle checkpoint signaling through the ATM and ATR kinasesGenes & Development, 2001