PUBLICATION

Udu deficiency activates DNA damage checkpoint

Authors
Lim, C.H., Chong, S.W., and Jiang, Y.J.
ID
ZDB-PUB-100105-1
Date
2009
Source
Molecular biology of the cell   20(19): 4183-4193 (Journal)
Registered Authors
Chong, Shang Wei, Jiang, Yun-Jin, Lim, Chiaw Hwee
Keywords
none
MeSH Terms
  • Mutation*
  • Body Patterning/genetics
  • Tumor Suppressor Protein p53/genetics
  • Tumor Suppressor Protein p53/metabolism
  • Embryo, Nonmammalian/embryology
  • Embryo, Nonmammalian/metabolism*
  • Immunohistochemistry
  • DNA Damage*
  • Heterochromatin/metabolism
  • Gene Expression Regulation, Developmental
  • Protein Serine-Threonine Kinases/genetics
  • Protein Serine-Threonine Kinases/metabolism
  • In Situ Hybridization
  • Protein Binding
  • Zebrafish/embryology
  • Zebrafish/genetics
  • Apoptosis/genetics
  • Erythroid-Specific DNA-Binding Factors/deficiency
  • Erythroid-Specific DNA-Binding Factors/genetics*
  • Erythroid-Specific DNA-Binding Factors/metabolism
  • Flow Cytometry
  • Animals
  • DNA Replication/drug effects
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics*
  • Zebrafish Proteins/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Bromodeoxyuridine/metabolism
  • Checkpoint Kinase 2
  • COS Cells
  • Two-Hybrid System Techniques
  • Cell Cycle/genetics
  • Chlorocebus aethiops
  • Microscopy, Fluorescence
PubMed
19656853 Full text @ Mol. Biol. Cell
Abstract
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.
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