title: Proliferative potential after DNA damage and non-homologous end joining are affected by loss of securin.
abstract: The faithful repair of DNA damage, especially chromosomal double-strand breaks (DSBs), is crucial for genomic integrity. We have previously shown that securin interacts with the Ku70/80 heterodimer of the DSB non-homologous DNA end-joining (NHEJ) repair machinery. Here we demonstrate that securin deficiency compromises cell survival and proliferation, but only after genotoxic stress. Securin(-/-) cells show a significant increase in gross chromosomal rearrangements and chromatid breaks after DNA damage, and also reveal an altered pattern of end resection in an NHEJ assay in comparison with securin(+/+) cells. These data suggest that securin has a key role in the maintenance of genomic stability after DNA damage, thereby providing a previously unknown mechanism for regulating tumour progression.
authors.affiliation: Centro Andaluz de Biología Molecular y Medicina Regenerativa, Isla de la Cartuja, Seville 41092, Spain.
authors.forename: J A
authors.initials: JA
authors.lastname: Bernal
authors.forename: M
authors.initials: M
authors.lastname: Roche
authors.forename: C
authors.initials: C
authors.lastname: Méndez-Vidal
authors.forename: A
authors.initials: A
authors.lastname: Espina
authors.forename: M
authors.initials: M
authors.lastname: Tortolero
authors.forename: J A
authors.initials: JA
authors.lastname: Pintor-Toro
mesh_terms: D001483:Base Sequence; D002166:Camptothecin / Q000494:pharmacology; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002869:Chromosome Aberrations; D004247:DNA / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004317:Doxorubicin / Q000494:pharmacology; D042822:Genomic Instability; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*; D064249:Securin
chemical_list: D009363:Neoplasm Proteins; D034741:RNA, Small Interfering; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human; D004317:Doxorubicin; D004247:DNA; D002166:Camptothecin