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

CASTRO PASCUAL, IVANNA CARLA; DAS NEVES OLIVEIRA, ANGELA; MELENDEZ, MATÍAS; CARGNELUTTI, ETHELINA; ALTAMIRANO, FERNANDO GABRIEL; FERRAMOLA, MARIANA LUCILA; LACOSTE, MARÍA GABRIELA; DELGADO, SILVIA MARCELA; ANZULOVICH, ANA CECILIA

Mendoza

Congreso; XL Reunión Científica Anual de la Sociedad de Biología de Cuyo; 2022

Sociedad de Biología de Cuyo

The circadian clock integrates external environmental changes with the internal physiology. Different studies have described a role of clock molecular machinery on the regulation of DNA repair mechanisms. In this sense, other authors reported a clock controlled modulation of DNA nucleotide excision repair. Accordingly, we previously reported evidence of circadian rhythmicity in the expression of genes involved in DNA base excision repair (BER) system, in 22-mo-old rats. BER is a key mechanism to avoid oxidative and alkylative DNA damage, which predisposes to different diseases such as cancer or neurodegenerative disorders. Our objective was to elucidate the molecular mechanisms involved in the control of the circadian expression of the enzymes involved in the BER system. Through in vitro transient transfection studies in NIH-3T3 cells, we assayed the response of the regulatory regions of Ogg1 and Ape1 genes to de BMAL1:CLOCK heterodimer. Previously, our bioinformatics studies revealed 13 E-box-like (CANNTG) and 5 perfect (CACGTG) E-box sites in regulatory regions of Ogg1 and Ape1, respectively. Subsequently, the bioluminescence assays showed that the BMAL1:CLOCK heterodimer exerted a differential regulation, activating the Luc expression driven by the regulatory region of Ogg1 (p