Elucidating the DNA Damage Pathway

For this article, Jennifer Fisher Wilson interviewed Thanos Halazonetis, molecular biologist at the Wistar Institute in Philadelphia; Tak Mak, departments of medical biophysics and immunology at University of Toronto; and Carol Prives, department of biological sciences at Columbia University in New York City. Data from the Web of Science (ISI, Philadelphia) show that Hot Papers are cited 50 to 100 times more often than the average paper of the same type and age. N.H. Chehab et al., "Chk2/hCds1 f

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During the 1990s, scientists identified the events downstream of p53 that lead to arrest or apoptosis. Little was known, however, about upstream signaling events that follow DNA damage leading to p53's activation and stabilization. This research led these authors to find the kinase that activates p53. Until this work, "we knew very little about the upstream p53 regulators, only that ATM [Ataxia telangiectasia-mutated] was involved," says Thanos Halazonetis, a molecular biologist at the Wistar Institute in Philadelphia and lead author of one of these papers.

Soon afterward, researcher Robert Abraham at Duke University Medical Center, Durham, NC, showed that another DNA damage sensor, ATR (ATM and Rad-3 related), also functions upstream of p53.4 But the findings suggested that some other kinase, activated by ATM and ATR, must stabilize p53 by phosphorylating on the gene's serine-20 (Ser-20) location.

Meanwhile, biochemist Steve Elledge, Baylor College of Medicine, Houston, cloned a kinase called ...

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