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How ATR turns on: TopBP1 goes on ATRIP with ATR

Department of Genetics, Center for Genetics and Genomics, Brigham and Women’s Hospital, Howard Hughes Medical Institute, Harvard Medical School, Boston, Massachusetts 02115, USA

In this issue of Genes & Development, Mordes and colleagues (pp. 1478–1489) reveal intriguing mechanistic insights into activation of the ATR (ATM and Rad3-related) kinase critical for DNA damage resistance. They identify conserved regulatory domains within ATR and its binding partner ATRIP (ATR-interacting protein), which are contacted by the ATR activator TopBP1. These discoveries expand on our understanding of the regulation of other PIKK family members, which also contain these domains, and illustrate how functional diversity has been achieved among these kinases.

[Keywords: ATR; ATRIP; TopBP1; checkpoint; PIKK; Ddc2]

E-MAIL selledge{at}genetics.med.harvard.edu; FAX (617) 525-4500.

Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.1685108.

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Related Article

TopBP1 activates ATR through ATRIP and a PIKK regulatory domain

Daniel A. Mordes, Gloria G. Glick, Runxiang Zhao, and David Cortez
Genes & Dev. 2008 22: 1478-1489. [Abstract] [Full Text] [PDF]