CLOCK’S DIFFERENTIAL TRANSCRIPTIONAL CONTROL ON OGG1 AND APE1 CIRCADIAN EXPRESSION

CASTRO PASCUAL, IC; DAS NEVES OLIVEIRA, A; MELENDEZ, M; CARGNELUTTI, E; ALTAMIRANO, FG; FERRAMOLA, M; LACOSTE, MG; DELGADO, MS; ANZULOVICH, AC

Congreso; XL REUNIÓN CIENTÍFICA ANUAL DE LA SOCIEDAD DE BIOLOGÍA DE CUYO; 2022

CLOCK’S DIFFERENTIAL TRANSCRIPTIONALCONTROL ON OGG1 AND APE1 CIRCADIAN EXPRESSIONCastroPascual IC¹, das Neves Oliveira A², Melendez M2,Cargnelutti E1,3, Altamirano FG¹, Ferramola ML3, LacosteMG¹, Delgado M3, Anzulovich AC1,31 Laboratorio de Cronobiología, IMIBIO-SL,CONICET-UNSL, San Luis, Argentina. 2 Centro de Pesquisa emOncologia Molecular, Hospital de Câncer de Barretos, São Paulo, Brasil. 3 Facultad de Química, Bioquímica y Farmacia, UNSL,San Luis, ArgentinaPresenting author: Ivanna Castro Pascual, ivannacastropascual@gmail.com The circadian clock integrates external environmental changes with the internal physiology. Different studies have described the clock molecular machinery and its regulatory circuits, as well as its role in the control of DNA repair mechanisms. In this sense, other authors reported a clock controlled modulation of DNA nucleotide excision repair. Accordingly, we previously reported evidenceof circadian rhythmicity in the expression of genes involved in DNA base excision repair (BER) system, in 22-mo-old rats. Our objective was to elucidatethe molecular mechanisms involved in the control of the circadian expression of the enzymes involved on the BER system. Through in vitro transient transfection studies of the NIH-3T3 cell line, we assayed the response of the regulatory regions of Ogg1 and Ape1 to de BMAL1:CLOCK heterodimer. Previously, our bioinformatics studies revealed that the regulatory regions of Ogg1 and Ape1 contained 13 E-box-like (CANNTG) and 5 perfect (CACGTG) E-box sites,respectively. Subsequently, bioluminescence assays showed that the BMAL1:CLOCK heterodimer exerted a differential regulation, activating the expression of luciferase driven by the regulatory region of Ogg1 (p<0.001), and repressing the expression driven by the regulatory region of Ape1 (p<0.01). The ability to anticipate and repair cyclical DNA damage is essential for protective functions of tissues, especially during aging, thus, our results would contribute to the growing evidence that circadian clocks may regulate the cellular response to DNA damage.