Circadian-independent cell mitosis in immortalized fibroblasts.
Two prominent timekeeping systems, the cell cycle, which controls cell division, and the circadian system, which controls 24-h rhythms of physiology and behavior, are found in nearly all living organisms. A distinct feature of circadian rhythms is that they are temperature-compensated such that the period of the rhythm remains constant (approximately 24 h) at different ambient temperatures. Even though the speed of cell division, or growth rate, is highly temperature-dependent, the cell-mitosis rhythm is temperature-compensated. Twenty-four-hour fluctuations in cell division have also been observed in numerous species, suggesting that the circadian system is regulating the timing of cell division. We tested whether the cell-cycle rhythm was coupled to the circadian system in immortalized rat-1 fibroblasts by monitoring cell-cycle gene promoter-driven luciferase activity. We found that there was no consistent phase relationship between the circadian and cell cycles, and that the cell-cycle rhythm was not temperature-compensated in rat-1 fibroblasts. These data suggest that the circadian system does not regulate the cell-mitosis rhythm in rat-1 fibroblasts. These findings are inconsistent with numerous studies that suggest that cell mitosis is regulated by the circadian system in mammalian tissues in vivo. To account for this discrepancy, we propose two possibilities: (i) There is no direct coupling between the circadian rhythm and cell cycle but the timing of cell mitosis is synchronized with the rhythmic host environment, or (ii) coupling between the circadian rhythm and cell cycle exists in normal cells but it is disconnected in immortalized cells.
Yeom
Mijung
M
Department of Biological Sciences, Vanderbilt University, Nashville, TN 37235-1634, USA.
Pendergast
Julie S
JS
Ohmiya
Yoshihiro
Y
Yamazaki
Shin
S
D000818:Animals; D002460:Cell Line; D002470:Cell Survival; D002940:Circadian Rhythm; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D005786:Gene Expression Regulation; D008938:Mitosis; D051381:Rats; D013696:Temperature
Methods Enzymol. 2005;393:288-301
15817295
FASEB J. 2005 Feb;19(2):304-6
15545298
Cell. 1983 Jun;33(2):389-96
6134587
Clin Cancer Res. 2007 Mar 1;13(5):1399-404
17332281
J Neurosci. 1999 Oct 1;19(19):8630-6
10493763
Cell Biol Int. 2001;25(2):179-83
11237422
J Pathol. 2005 May;206(1):111-20
15809976
Science. 1981 Mar 6;211(4486):1002-13
7008196
J Biol Chem. 1995 Nov 24;270(47):28419-24
7499347
PLoS Comput Biol. 2006 Oct;2(10):e136
17040123
Neuroreport. 1998 Apr 20;9(6):1001-5
9601657
Science. 1998 Jun 5;280(5369):1599-603
9616122
Hum Mol Genet. 2006 Oct 15;15 Spec No 2:R271-7
16987893
Cell. 1998 Jun 12;93(6):929-37
9635423
Cell. 2000 Dec 22;103(7):1009-17
11163178
Carcinogenesis. 2005 Jul;26(7):1241-6
15790588
Cell. 1994 Nov 18;79(4):563-71
7954823
Cell. 1999 Jul 23;98(2):193-205
10428031
Cell. 1989 Sep 8;58(5):833-46
2570636
Exp Cell Res. 1985 Mar;157(1):144-58
3918876
Curr Biol. 2002 Apr 2;12(7):551-7
11937023
Nature. 1963 Aug 31;199:863
14079893
Anat Rec. 1983 Mar;205(3):239-49
6837940
Am J Pathol. 2001 May;158(5):1793-801
11337377
Curr Biol. 2000 Oct 19;10(20):1291-4
11069111
Int J Radiat Oncol Biol Phys. 1994 Jan 1;28(1):135-44
8270434
Photochem Photobiol. 1999 Aug;70(2):254-60
10461465
Biochem Biophys Res Commun. 2002 Jan 25;290(3):933-41
11798163
Cancer Res. 2007 Aug 15;67(16):7917-22
17699798
Blood. 2005 Oct 15;106(8):2827-36
15985538
Annu Rev Physiol. 1993;55:16-54
8466172
J Cell Biol. 1995 May;129(4):1061-9
7744955
Acta Anat (Basel). 1974;88(3):411-23
4854750
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):16089-94
14657355
Cell. 2002 Jul 12;110(1):107-17
12151001
Neoplasia. 2007 Oct;9(10):797-800
17971899
Exp Cell Res. 1982 Aug;140(2):307-13
7117394
J Biol Rhythms. 2008 Feb;23(1):95-8
18258762
Anat Rec. 1978 Aug;191(4):479-86
697058
J Biol Chem. 1998 Nov 20;273(47):31505-9
9813064
J Biol Chem. 2002 Sep 27;277(39):36009-17
12130638
Dialogues Clin Neurosci. 2007;9(3):257-72
17969863
Cell. 2004 Nov 24;119(5):693-705
15550250
Cell. 1999 Jan 8;96(1):57-68
9989497
Prog Cell Cycle Res. 1996;2:241-66
9552400
FEBS Lett. 2000 Jan 7;465(1):79-82
10620710
Am J Anat. 1983 Dec;168(4):433-65
6320626
EMBO J. 2009 Jan 21;28(2):123-34
19078963
J Invest Dermatol. 1991 Aug;97(2):273-80
1830075
Mol Cell Biol. 1997 Jul;17(7):3687-93
9199302
Am J Pathol. 1999 Feb;154(2):613-22
10027418
Cell Cycle. 2009 Mar 15;8(6):832-7
19221497
Genes Cells. 2003 Aug;8(8):713-20
12875656
Curr Biol. 2004 Dec 29;14(24):2289-95
15620658
Annu Rev Biochem. 1992;61:441-70
1497317
Genes Cells. 1998 Mar;3(3):167-76
9619629
EMBO J. 1995 Feb 1;14(3):603-9
7859748
Nature. 1999 Jul 8;400(6740):169-73
10408444
Cancer Sci. 2006 Dec;97(12):1298-307
16999817
Nature. 1997 Oct 2;389(6650):512-6
9333243
Blood. 1991 Jun 15;77(12):2603-11
2043764