Coupling of human circadian and cell cycles by the timeless protein.
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.
Unsal-Kaçmaz
Keziban
K
Department of Biochemistry and Biophysics, Mary Ellen Jones Building CB 7260, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Mullen
Thomas E
TE
Kaufmann
William K
WK
Sancar
Aziz
A
D048868:Adaptor Proteins, Signal Transducing; D064007:Ataxia Telangiectasia Mutated Proteins; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D000071877:Checkpoint Kinase 1; D042002:Chromatin Assembly and Disassembly / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D056931:Cryptochromes; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects / Q000502:physiology; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000187:drug effects; D005090:Exodeoxyribonucleases / Q000378:metabolism; D005420:Flavoproteins / Q000378:metabolism; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C521194:ATRIP protein, human; D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D004268:DNA-Binding Proteins; D005420:Flavoproteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C509769:TIMELESS protein, human; C509770:Timeless protein, mouse; D014157:Transcription Factors; D011494:Protein Kinases; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1; C000605869:Chek1 protein, mouse; D017346:Protein Serine-Threonine Kinases; D005090:Exodeoxyribonucleases; C429526:three prime repair exonuclease 1; D006918:Hydroxyurea