title: Coupling of human circadian and cell cycles by the timeless protein.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, Mary Ellen Jones Building CB 7260, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Keziban
authors.initials: K
authors.lastname: Unsal-Kaçmaz
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Mullen
authors.forename: William K
authors.initials: WK
authors.lastname: Kaufmann
authors.forename: Aziz
authors.initials: A
authors.lastname: Sancar
mesh_terms: 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*
chemical_list: 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