Visit our Expo - Redox and Inflammation signaling 2012

Session XVII : Cell signaling in health and disease Poster XVII, 14
Menin protracts Chk1 phosphorylation and increases the ratio of homology-directed
DNA repair
Esposito I.1, Gallo A.2, Terrazzano G.1 and Musti A.M.1,3
1 Dip.Biol.Patol.Cell.Mol., University of Naples “FedericoII, Italy
2 I.E.O.S. of CNR c/o University of Naples “FedericoII”, Italy
3 Dip. Farmaco-biologico, University of Calabria, Rende (Cs), Italy
Multiple Endocrine Neoplasia type 1 (MEN1) is an inherited tumor disease characterised by
pancreatic, parathyroid and anterior pituitary adenomas Besides, many MEN-1 patients also
develop tumors in a range of non-endocrine tissues, suggesting that MEN1 may control tumor
development in different tissues, depending on genetic interactions with other cancerassociated
genes. Menin, the nuclear protein encoded by the MEN1 gene, interacts with a
large number of proteins, among which nuclear proteins involved in chromatin modification
or DNA repair, as Tritorax, RPA and FANCD2. Besides, loss of menin expression leads to
increased sensitivity to DNA damage, both in embryonic mouse fibroblasts and Drosophila
larvae.
We have investigated the effect of Menin over-expression on the cellular response to DNA
damage. We found that menin protracts the ATM/ATR-dependent phosphorylation of the Sphase
checkpoint kinase Chk1, in response to etoposide or UV radiation, without affecting the
rate of DNA damage. However, menin-induced persistence of Chk1 activation had no effect
on either etoposide-induced S-phase arrest or apoptosis, but increased the ratio of
homologous-directed DNA repair. These results provide novel insights into the
oncosuppressor activity of MEN-1 by linking menin to DNA-repair pathways.
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