Journal of Cell and Molecular Biology - ResearchGate

Journal of Cell and Molecular Biology 9(2):1-10, 2011 Review Article 1
Haliç University, Printed in Turkey.
http://jcmb.halic.edu.tr
Kanserde sirkadiyan ritim genlerinin rolü
The role of circadian rhythm genes in cancer
Harika ATMACA and Selim UZUNOĞLU *
Celal Bayar University, Faculty of Arts and Sciences, Department of Biology, Manisa, Turkey.
(* author for correspondenceselim@bayar.edu.tr)
Received: 27 October 2011; Accepted: 9 December 2011
Abstract
Circadian (In Latin: Circa=around, Diem=day) rhythm describes the processes of 24 hour oscillations
in the living systems. At the cellular level, circadian rhythm is controlled by a molecular network with
positive and negative feedbacks. The known critical elements in the positive feedback loop are Clock
and Bmal1; the ones in complementary negative feedback are mainly Period and Cryptochrome genes.
In cancer, which is an important health problem today, dysregulation of circadian rhythm is an
important risk factor. In this review, circadian rhythm genes involved in cell proliferation, apoptosis,
DNA repair, metabolism, detoxification and response to DNA damage and their roles in cancer
development are summarized.
Keywords: Circadian rhythm, cancer, period, cryptochrome, molecular clock
Özet
Sirkadiyan (Latince: circa=yaklaşık, diem=gün) ritim canlı sistemlerdeki 24 saatlik dalgalanmalara
maruz olayları tanımlar. Hücresel seviyede bakıldığında sirkadiyan ritim, pozitif ve negatif
geribildirimler içeren moleküler ağ bir tarafından kontrol edilir. Pozitif geribildirim döngüsünde
bilinen kritik elementler Clock ve Bmal1, tamamlayıcı negatif geribildirimde ise Period ve
Cryptochrome genleridir. Günümüzde önemli bir sağlık sorunu olan kanserde sirkadiyan ritmin
bozulması önemli bir risk faktörüdür. Bu derlemede hücre çoğalması, apoptoz, DNA tamiri,
metabolizma, detoksifikasyon ve DNA hasarına cevapla ilişkili sirkadiyan ritim genleri ve kanser
oluşumundaki rolleri özetlenmiştir.
Anahtar Sözcükler: Sirkadiyan ritim, kanser, periyot, kriptokrom, moleküler saat
Kısaltmalar listesi
Clock: Circadian Locomotor Output Cycles Kaput, Bmal1: Brain-muscle-arnt-like 117 protein 1,
CRY: Cryptochrome, PER: Period homolog 1, E-box: Enhancer box, ROR: Retinoid-related orphan
receptor-alpha, REV-ERBα: Nuclear receptor Rev-ErbA-alpha, NONO: Non-POU domain containing,
octamer-binding, DEC: Deleted in esophageal cancer 1, CYP2A5: Cytochrome P450 2A5, CYP2C50:
Cytochrome P450 2C50, CES3: Carboxylesterase 3, MDR1: ATP-binding cassette, sub-family B
(MDR/TAP), member 1, Npas2: Neuronal PAS domain protein 2, Fas: TNF receptor superfamily,
member 6, Bax: BCL2-associated X protein, c-myc: Cell division cycle associated 7, Chk1: CHK1
checkpoint homolog, Chk2: CHK2 checkpoint homolog, Atr1: Ataxia telangiectasia and Rad3 related,
Jak2: Janus kinase 2, ER: Estrogen receptor, Pbef: Pre- B- cell colony- enhancing factor, Akt1: V-akt
murine thymoma viral oncogene homolog 1, Cdk2: Cyclin-dependent kinase 2, TGFβ: Transforming
growth factor, beta, EGF: Epidermal growth factor, CCL5: Chemokine (C-C motif) ligand 5,
BDKRB2: Bradykinin receptor B2, SP100: SP100 nuclear antigen, Wee1: WEE1 homolog, Mdm-2:
Mdm2 p53 binding protein homolog (mouse), Gadd45: Growth arrest and DNA-damage-inducible