Biotechnology and Circadian Clock LAB
Gizem’s paper is published in Journal of Biological Chemistry. This paper is entitled “Functional characterization of the CRY2 circadian clock component variant p.Ser420Phe revealed a new degradation pathway for CRY2” and describes a new degradation pathway for Cryptochrome 2.
Onur’s paper is published in Journal of Biomolecular Structure and Dynamics. This paper is entitled “Dynamic regulation of the serine loop by distant mutations reveals allostery in cryptochrome 1” and highlights the importance of allosteric regulation in CRY1 for the CLOCK interaction
Effects of mutations on mutant and wild type CRY PHR domains
Saliha’s PhD work is published in Biochemical Pharmacology. The paper is about discovery of a molecule (TW68), which stabilize both mammalian Cryptochromes. Saliha showed TW68 control fasting blood glucose level in diabetic animals through the control of gluconeogenesis.
Our book chapter published in Advances in Protein Chemistry and Structural Biology. This chapter is entitled “Single nucleotide polymorphisms (SNPs) in circadian genes: Impact on gene function and phenotype” and we summarize the effect of core clock gene SNPs on circadian rhythm and diseases in humans .
Kübra’s paper is published in Journal of Biological Rhythm. This paper is entitled “Diurnal Changes in Capecitabine Clock-Controlled Metabolism Enzymes Are Responsible for Its Pharmacokinetics in Male Mice” and highlights the importance of capecitabine administration time to increase the efficacy with minimum adverse effects .
Barış’s paper is published in Journal of Biological Chemistry. This paper is entitled “The crystal structure of Vibrio cholerae (6-4) photolyase reveals interactions with cofactors and a DNA binding region” and describes crystal structure of Vc (6-4) photolyase .
Şerefs’ paper is published in Nature Communications. This paper is entitled “Discovery of a small molecule that selectively destabilizes Cryptochrome 1 and enhances life span in p53 knockout mice” and describes discovery of a molecule, M47, selectively reduces half- life of mammalian Cryptochrome 1.
(A) Ras pT24 transformed p53 null MSF fibroblast cells were treated with 0, 10 or 20µM oxaliplatinand incubated for 24h. Then either DMSO or M47 was added and incubated for 16h. Cells were lysed, and protein levels were analyzed by Western blot. In each case, M47 increases the cleaved PARP protein level and decreases CRY1 levels. Bar graph was drawn normalizing to 10µM dosage of oxaliplatin (Data represent the mean ± SEM, n=4, **p=0.0051versus DMSO control by two-way ANOVA). (B) Measurement of Caspase-3 activity in WT or p53-null Ras-transformed MSF cells (p53-null) treated with oxaliplatin in the absence (DMSO) and presence of M47. Cells were treated with DMSO or M47 (5 μM) for 24h and then 0, 10, 20 μM oxaliplatin for 16h. Caspase-3 activity in total cell lysates was measured using the Caspase-3 substrate, Z-DEVD-R110. The activity was normalized to total protein concentration and presented as fold activity to 0 μM treated samples. The results are the average of 3 biological replicates± SEM (**p=0.0077 versus M47 treated cells with one-way ANOVA with Dunnet’s post hoc test). (C) M47in p53-/- mice increases age-adjusted incidence of survival. Kaplan–Meier survival analysis (log-rank test) of the time of death with evidence of tumors showed significant differences between vehicle-treated p53-/- and M47-treated p53-/- (**p=0.0068) (n=9 for vehicle-treated and n=7 for the M47 treated). Arrow indicates M47 administration (18th week).
Gizem’s paper is published in Journal of Biological Chemistry. This paper is entitled “The secondary pocket of Cryptochrome 2 is important for the regulation of its stability and localization” and describes the importance of the rim of the secondary packet in CRY2 function.
Our book chapter titled “The Structure-Based Molecular-Docking Screen Against Core Clock Proteins to Identify Small Molecules to Modulate the Circadian Clock” is published Methods in Molecular Biology.
Our book chapter titled “Protein interaction networks of the mammalian core clock proteins” is published in Advances in Protein Chemistry and Structural Biology.
