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Reconstitution of a human ATR-mediated checkpoint response to damaged DNA

Reconstitution of a human ATR-mediated checkpoint response to damaged DNA

Authors :
Choi, Jun-Hyuk
Lindsey-Boltz, Laura A.
Sancar, Aziz
Source :
Proceedings of the National Academy of Sciences of the United States. August 14, 2007, Vol. 104 Issue 33, p13301, 6 p.
Publication Year :
2007

Abstract

The DNA damage checkpoint response delays cell cycle progression upon DNA damage and prevents genomic instability. Genetic analysis has identified sensor, mediator, signal transducer, and effector components of this global signal transduction pathway. Here we describe an in vitro system with purified human check-point proteins that recapitulates key elements of the DNA damage checkpoint. We show that the damage sensor ATR in the presence of topoisomerase II binding protein 1 (TopBP1) mediator/adaptor protein phosphorylates the Chk1 signal-transducing kinase in a reaction that is strongly dependent on the presence of DNA containing bulky base lesions. The dependence on damaged DNA requires DNA binding by TopBP1, and, indeed, TopBP1 shows preferential binding to damaged DNA. This in vitro system provides a useful platform for mechanistic studies of the human DNA damage checkpoint response. Chk1 kinase | damage recognition | signal transduction | topoisomerase II binding protein 1

Details

Language :
English
ISSN :
00278424
Volume :
104
Issue :
33
Database :
Gale General OneFile
Journal :
Proceedings of the National Academy of Sciences of the United States
Publication Type :
Academic Journal
Accession number :
edsgcl.168334352