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Vol. 20, Issue 19, 4183-4193, October 1, 2009

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Udu Deficiency Activates DNA Damage Checkpoint

Chiaw-Hwee Lim^*, Shang-Wei Chong^*, and Yun-Jin Jiang^*,,

*Laboratory of Developmental Signalling and Patterning, Genes and Development Division, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673; Department of Biochemistry, National University of Singapore, Singapore 117597; and School of Biological Sciences, Nanyang Technological University, Singapore 637551

Submitted February 5, 2009; Revised July 9, 2009; Accepted July 27, 2009
Monitoring Editor: Orna Cohen-Fix

Udu has been shown to play an essential role during blood cell development; however, its roles in other cellular processes remain largely unexplored. In addition, ugly duckling (udu) mutants exhibited somite and myotome boundary defects. Our fluorescence-activated cell sorting analysis also 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^tu24 mutants. We further showed that the extensive p53-dependent apoptosis in udu^tu24 mutants is a consequence of activation in the Atm–Chk2 pathway. Udu seems 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 is colocalized with 5-bromo-2'-deoxyuridine and heterochromatin during DNA replication, suggesting a role in maintaining genome integrity.

Address correspondence to: Yun-Jin Jiang (yjjiang{at}imcb.a-star.edu.sg).

Abbreviations used: ATM, Ataxia telangiectasia mutated; ATR, ATM- and Rad3-related; Chk, checkpoint kinase; GADD45, growth-arrest and DNA damage-inducible 45; hpf, hours postfertilization; MCM, minichromosome maintenance; MO, morpholino; PAH-L, paired amphipathic -helix like; pH3, phosphorylated histone H3; SANT-L, SW13, ADA2, N-Cor and TFIIIB like; ss, somite stage; udu, ugly duckling