Udu (Ugly duckling) has been first identified from a zebrafish mutant and shown to play an essential role during erythroid development; however, its roles in other cellular processes remain largely unexplored. FACS analysis showed that the loss of udu function resulted in defective cell cycle progression and comet assay indicated the presence of increased DNA damage in udu mutants. We further showed that the extensive p53-dependent apoptosis found in udu mutants is a consequence of activation in the Atm-Chk2 pathway. Udu appears not to be required for DNA repair, because both wild-type and udu embryos similarly respond to and recover from UV treatment. Yeast two-hybrid and coimmunoprecipitation data demonstrated that PAH-L repeats and SANT-L domain of Udu interacts with MCM3 and MCM4. Furthermore, Udu was colocalized with BrdU and heterochromatin during DNA replication, suggesting a role in maintaining genome integrity.Recently, we started to work on the second zebrafish homolog, Udu2, and its mammalian counterpart, Gon4l. Preliminary data showed that udu2 and Gon4l mRNA injection can rescue zebrafish udu mutant phenotypes. Furthermore, PAH-L and SANT-L domains of Udu2 and Gon4l can bind to MCM3 and MCM4 and they are localized in the nucleus. These data suggest that Udu2 and Gon4l are functionally equivalent to zebrafish Udu. Their molecular mechanism leading to udu phenotypes is currently under investigation.
Date:
2011-08
Relation:
European Biophysics Journal with Biophysics Letters. 2011 Aug;40(Suppl. 1):S97.
