RRC ID 3382
Author Garcia-Muse T, Boulton SJ.
Title Distinct modes of ATR activation after replication stress and DNA double-strand breaks in Caenorhabditis elegans.
Journal EMBO J.
Abstract ATM and ATR are key components of the DNA damage checkpoint. ATR primarily responds to UV damage and replication stress, yet may also function with ATM in the checkpoint response to DNA double-strand breaks (DSBs), although this is less clear. Here, we show that atl-1 (Caenorhabditis elegans ATR) and rad-5/clk-2 prevent mitotic catastrophe, function in the S-phase checkpoint and also cooperate with atm-1 in the checkpoint response to DSBs after ionizing radiation (IR) to induce cell cycle arrest or apoptosis via the cep-1(p53)/egl-1 pathway. ATL-1 is recruited to stalled replication forks by RPA-1 and functions upstream of rad-5/clk-2 in the S-phase checkpoint. In contrast, mre-11 and atm-1 are dispensable for ATL-1 recruitment to stalled replication forks. However, mre-11 is required for RPA-1 association and ATL-1 recruitment to DSBs. Thus, DNA processing controlled by mre-11 is important for ATL-1 activation at DSBs but not following replication fork stalling. We propose that atl-1 and rad-5/clk-2 respond to single-stranded DNA generated by replication stress and function with atm-1 following DSB resection.
Volume 24(24)
Pages 4345-55
Published 2005-12-21
DOI 10.1038/sj.emboj.7600896
PII 7600896
PMID 16319925
PMC PMC1356337
MeSH Animals Apoptosis Ataxia Telangiectasia Mutated Proteins Caenorhabditis elegans Caenorhabditis elegans Proteins / metabolism Caenorhabditis elegans Proteins / physiology* Cell Cycle Cell Nucleus / metabolism DNA Damage* DNA Replication* Meiosis Microscopy, Fluorescence Mitosis Models, Biological Models, Genetic Mutation Phosphotransferases / metabolism Phosphotransferases / physiology* Protein Structure, Tertiary RNA Interference Radiation, Ionizing Recombination, Genetic Repressor Proteins / metabolism S Phase Telomere-Binding Proteins / metabolism Time Factors Tumor Suppressor Protein p53 / metabolism Ultraviolet Rays
IF 11.227
Times Cited 114
C.elegans tm853