Biomedical Research

Investigation into the mechanism regulating mitotic DNA synthesis (MiDAS)

Joint Event on 2^nd International Conference on Tissue Science and Molecular Biology, Stem Cells & Separation Techniques
June 06-07, 2019 | London, UK

Jedrzej J Jaworski and Fumiko Esashi

University of Oxford, UK

Posters & Accepted Abstracts : Biomed Res

Abstract:

All multicellular organisms develop via proliferationdependent growth, which requires full genome duplication for each mitotic division. Cells with unreplicated DNA fragments may occasionally proceed to mitosis by bypassing canonical checkpoint activation. The resulting under-replicated regions are particularly prevalent following replication stress, as seen for instance, in cancer cells. They can be fixed by a recently characterized mechanism-mitotic DNA synthesis (MiDAS). Here, we investigate the upstream regulation of this process in osteosarcoma cells following induction of aphidicolinmediated replicative stress and cell synchronisation. Candidate components of the cell-cycle regulating machinery were ablated using RNAi and MiDAS was quantified using EdU incorporation during mitosis. Collectively, our results expose a vital role of BRCA2 and the UBR5 complex in regulating MiDAS, which facilitates a last-resort protective response to unreplicated genome regions in mitosis. Mechanistically, we propose that BRCA2-mediated RAD51 phosphorylation and UBR5-dependent chromatin clearance promote MiDAS. Our results uncover new potential factors that could be exploited therapeutically in cancer treatment.

Biography:

E-mail:

Jedrej.jaworski@st-hugs.ox.ac.uk

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