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Molecular and Cellular Biology, April 2005, p. 3109-3116, Vol. 25, No. 8
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.8.3109-3116.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Coupling of Human Circadian and Cell Cycles by the Timeless Protein

Keziban Ünsal-Kaçmaz,1 Thomas E. Mullen,2 William K. Kaufmann,3 and Aziz Sancar1*

Department of Biochemistry and Biophysics,1 Cancer Cell Biology Training Program,2 Department of Pathology and Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina3

Received 22 November 2004/ Returned for modification 6 January 2005/ Accepted 25 January 2005

The Timeless protein is essential for circadian rhythm in Drosophila. The Timeless orthologue in mice is essential for viability and appears to be required for the maintenance of a robust circadian rhythm as well. We have found that the human Timeless protein interacts with both the circadian clock protein cryptochrome 2 and with the cell cycle checkpoint proteins Chk1 and the ATR-ATRIP complex and plays an important role in the DNA damage checkpoint response. Down-regulation of Timeless in human cells seriously compromises replication and intra-S checkpoints, indicating an intimate connection between the circadian cycle and the DNA damage checkpoints that is in part mediated by the Timeless protein.

* Corresponding author. Mailing address: Department of Biochemistry and Biophysics, Mary Ellen Jones Building CB 7260, University of North Carolina School of Medicine, Chapel Hill, NC 27599. Phone: (919) 962-0115. Fax: (919) 843-8627. E-mail: Aziz_Sancar{at}med.unc.edu.

Molecular and Cellular Biology, April 2005, p. 3109-3116, Vol. 25, No. 8
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.8.3109-3116.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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