ALT-EJ GENERA REARREGLOS CROMOSÓMICOS EN RESPUESTA A ETOPÓSIDO EN CÉLULAS HUMANAS CON LOS PRINCIPALES SISTEMAS DE REPARACIÓN DE RUPTURAS DE DOBLE CADENA COMPROMETIDOS

نویسندگان

چکیده

The antitumor drug Etoposide (ETO) induces DNA double-strand breaks (DSB) and is associated with the development of secondary neoplasms in treated patients. DSB are repaired by two main mechanisms, homologous recombination (HR) classical non-homologous end joining (c-NHEJ). When HR c-NHEJ defective, PARP-1-dependent alternative end-joining (alt-EJ) pathway. involvement alt-EJ progression induced ETO G2 phase human cells was analyzed. HeLa deficient (cohesin RAD21 inhibition, RAD21kd) their non-silencing control (HeLa NS) were established. Cells presence a chemical inhibitor DNA-PKcs (DNA-PKi, c-NHEJ). In both cell lines, ETO-induced (γH2AX+) increased compared to controls. incorrect repair DNA-PKcs- RAD21-deficient caused synergistic augment chromatid exchanges dicentric chromosomes first second metaphase, respectively. contrast, frequency reduced PARP-1-deficient PARP-1kd) following treatment. RAD21kd binucleated cells, DNA-PKi/ETO percentage ≥20 γH2AX foci G1-postmitotic micronuclei at 96 h. A greater accumulation G2/M observed NS 8 cycle restarted 16 h; however, maintained RAD21kd. Chromosomal rearrangements obtained when absent decrease PARP-1kd suggest that contributes formation. Key words: chromosomal aberrations, cycle, cohesin, breaks, pathways

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ژورنال

عنوان ژورنال: BAG. Journal of basic and applied genetics

سال: 2023

ISSN: ['1666-0390', '1852-6233']

DOI: https://doi.org/10.35407/bag.2023.34.01.04