Open AccessCoupling of Human Circadian and Cell Cycles by the Timeless Protein
Author(s) -
Keziban Ünsal-Kaçmaz,
Thomas E. Mullen,
William K. Kaufmann,
Aziz Sancar
Publication year - 2005
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.25.8.3109-3116.2005
Subject(s) - timeless , biology , cryptochrome , circadian rhythm , circadian clock , microbiology and biotechnology , bacterial circadian rhythms , cell cycle , cell cycle checkpoint , genetics , cell , neuroscience
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.