Recruitment of ATR-ATRIP, Rad17, and 9-1-1 complexes to DNA damage.
The ATR (ataxia-telangiectasia mutated and rad3-related)-ATRIP (ATR-interacting protein) kinase complex plays a central role in the checkpoint responses to a variety of types of DNA damage, especially those interfering with DNA replication. The checkpoint-signaling pathway activated by ATR-ATRIP regulates and coordinates cell-cycle progression, DNA replication, DNA repair, and many other cellular processes critical for genomic stability. Upon DNA damage or DNA replication interference, ATR-ATRIP and two of its key regulators, the Rad17 and the 9-1-1 complexes, are localized to sites of DNA damage and stalled replication forks. Recent biochemical and cell biological studies have revealed that RPA-coated single-stranded DNA, a common structure generated at sites of DNA damage and stalled replication forks, plays crucial roles in the recruitment of ATR-ATRIP, Rad17, and 9-1-1 complexes. The recruitment of ATR-ATRIP and its regulators to DNA damage is a key step for the recognition of DNA damage by the checkpoint, and is likely important for the regulation of ATR activity and/or function in response to DNA damage. The methods used to characterize the DNA association of ATR-ATRIP, Rad17, and 9-1-1 complexes have laid a foundation for further biochemical studies, which may ultimately lead us to understand the molecular mechanisms by which ATR-ATRIP monitors and protects genomic integrity.
Yang
Xiaohong Helena
XH
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, USA.
Zou
Lee
L
D018797:Cell Cycle Proteins / Q000302:isolation & purification / Q000378:metabolism*; D004249:DNA Damage; D004261:DNA Replication; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000302:isolation & purification / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000302:isolation & purification / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000302:isolation & purification / Q000378:metabolism*
C108080:ATR1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; D009687:Nuclear Proteins; C501395:RAD17 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins