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|Title:||A new role for Drosophila Aurora-A in maintaining chromosome integrity||Authors:||Merigliano, Chiara
|Keywords:||Science::Biological sciences||Issue Date:||2019||Source:||Merigliano, C., Mascolo, E., Cesta, A., Saggio, I. & Vernì, F. (2019). A new role for Drosophila Aurora-A in maintaining chromosome integrity. Chromosoma, 128(1), 41-52. https://dx.doi.org/10.1007/s00412-018-00687-0||Journal:||Chromosoma||Abstract:||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, in Drosophila, and we showed that it causes chromosome aberrations (CABs). In addition, aur-A949 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-A949 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-A949 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-A949. Based on studies in other systems, which show that phosphorylation is important to target Lig4 for degradation, we hypothesized that in aur-A949 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.||URI:||https://hdl.handle.net/10356/151271||ISSN:||0009-5915||DOI:||10.1007/s00412-018-00687-0||Rights:||© 2019 Springer-Verlag GmbH Germany, part of Springer Nature. All rights reserved.||Fulltext Permission:||none||Fulltext Availability:||No Fulltext|
|Appears in Collections:||SBS Journal Articles|
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