ATR signalling: more than meeting at the fork.

Nam EA, Cortez D
Biochem J. 2011 436 (3): 527-36

PMID: 21615334 · PMCID: PMC3678388 · DOI:10.1042/BJ20102162

Preservation of genome integrity via the DNA-damage response is critical to prevent disease. ATR (ataxia telangiectasia mutated- and Rad3-related) is essential for life and functions as a master regulator of the DNA-damage response, especially during DNA replication. ATR controls and co-ordinates DNA replication origin firing, replication fork stability, cell cycle checkpoints and DNA repair. Since its identification 15 years ago, a model of ATR activation and signalling has emerged that involves localization to sites of DNA damage and activation through protein-protein interactions. Recent research has added an increasingly detailed understanding of the canonical ATR pathway, and an appreciation that the canonical model does not fully capture the complexity of ATR regulation. In the present article, we review the ATR signalling process, focusing on mechanistic findings garnered from the identification of new ATR-interacting proteins and substrates. We discuss how to incorporate these new insights into a model of ATR regulation and point out the significant gaps in our understanding of this essential genome-maintenance pathway.

MeSH Terms (20)

Adaptor Proteins, Signal Transducing Animals Ataxia Telangiectasia Ataxia Telangiectasia Mutated Proteins BH3 Interacting Domain Death Agonist Protein Carrier Proteins Cell Cycle Proteins DNA-Binding Proteins DNA Damage DNA Helicases DNA Repair Humans MutL Protein Homolog 1 MutS DNA Mismatch-Binding Protein Nuclear Proteins Protein-Serine-Threonine Kinases Protein Processing, Post-Translational Protein Structure, Tertiary Proto-Oncogene Proteins c-ets Signal Transduction

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