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June 06-07, 2019 | London, UK
2nd International Conference on
Tissue Science and Molecular Biology,
Stem Cells & Separation Techniques
Joint Event
Biomedical Research (An International Journal of Medical Sciences) | ISSN: 0976-1683 Volume 30
Investigation into the mechanism regulating mitotic DNA synthesis (MiDAS)
Jedrzej J Jaworski and Fumiko Esashi
University of Oxford, UK
All multicellular organisms develop via proliferation-
dependent growth, which requires full genomeduplication
foreachmitoticdivision.CellswithunreplicatedDNAfragments
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 aphidicolin-
mediated 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.
e:
Biomed Res, Volume 30
ISSN: 0976-1683