ATM and related protein kinases: safeguarding genome integrity

Y Shiloh - Nature reviews cancer, 2003 - nature.com
Nature reviews cancer, 2003nature.com
Maintenance of genome stability is essential for avoiding the passage to neoplasia. The
DNA-damage response—a cornerstone of genome stability—occurs by a swift transduction
of the DNA-damage signal to many cellular pathways. A prime example is the cellular
response to DNA double-strand breaks, which activate the ATM protein kinase that, in turn,
modulates numerous signalling pathways. ATM mutations lead to the cancer-predisposing
genetic disorder ataxia-telangiectasia (AT). Understanding ATM's mode of action provides …
Abstract
Maintenance of genome stability is essential for avoiding the passage to neoplasia. The DNA-damage response — a cornerstone of genome stability — occurs by a swift transduction of the DNA-damage signal to many cellular pathways. A prime example is the cellular response to DNA double-strand breaks, which activate the ATM protein kinase that, in turn, modulates numerous signalling pathways. ATM mutations lead to the cancer-predisposing genetic disorder ataxia-telangiectasia (A-T). Understanding ATM's mode of action provides new insights into the association between defective responses to DNA damage and cancer, and brings us closer to resolving the issue of cancer predisposition in some A-T carriers.
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