Aurora-A is a conserved mitotic kinase overexpressed in many types of cancer. Growing evidence shows that Aurora-A plays a crucial role in DNA damage response (DDR) although this aspect has been less characterized. We isolated a new aur-A mutation, named aur-A949, inDrosophila, and we showed that it causes chromosome aberrations (CABs). In addition, aur-A 949 mutants were sensitive to X-ray treatment and showed impaired γ-H2Av foci dissolution kinetics. To identify the pathway in which Aur-A works, we conducted an epistasis analysis by evaluating CAB frequencies in double mutants carrying aur-A 949 mutation combined to mutations in genes related to DNA damage response (DDR). We found that mutations in tefu (ATM) and in the histone variant H2Av were epistatic over aur-A 949 indicating that Aur-A works in DDR and that it is required for γ-H2Av foci dissolution. More interestingly, we found that a mutation in lig4, a gene belonging to the non-homologous end joining (NHEJ) repair pathway, was epistatic over aur-A 949. Based on studies in other systems, which show that phosphorylation is important to target Lig4 for degradation, we hypothesized that in aur-A 949 mutant cells, there is a persistence of Lig4 that could be, in the end, responsible for CABs. Finally, we observed a synergistic interaction between Aur-A and the homologous recombination (HR) repair system component Rad 51 in the process that converts chromatid deletions into isochromatid deletions. Altogether, these data indicate that Aur-A depletion can elicit chromosome damage. This conclusion should be taken into consideration, since some anticancer therapies are aimed at reducing Aurora-A expression.
A new role for Drosophila Aurora-A in maintaining chromosome integrity / Merigliano, Chiara; Mascolo, Elisa; Cesta, Anthony; Saggio, Isabella; Vernì, Fiammetta. - In: CHROMOSOMA. - ISSN 0009-5915. - 128(2019), pp. 41-52.
|Titolo:||A new role for Drosophila Aurora-A in maintaining chromosome integrity|
MERIGLIANO, CHIARA (Primo)
MASCOLO, Elisa (Secondo)
SAGGIO, Isabella (Corresponding author)
VERNI', Fiammetta (Corresponding author)
|Data di pubblicazione:||2019|
|Citazione:||A new role for Drosophila Aurora-A in maintaining chromosome integrity / Merigliano, Chiara; Mascolo, Elisa; Cesta, Anthony; Saggio, Isabella; Vernì, Fiammetta. - In: CHROMOSOMA. - ISSN 0009-5915. - 128(2019), pp. 41-52.|
|Appartiene alla tipologia:||01a Articolo in rivista|