Udu deficiency activates DNA damage checkpoint

Mol Biol Cell. 2009 Oct;20(19):4183-93. doi: 10.1091/mbc.e09-02-0109. Epub 2009 Aug 5.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Body Patterning / genetics
  • Bromodeoxyuridine / metabolism
  • COS Cells
  • Cell Cycle / genetics
  • Checkpoint Kinase 2
  • Chlorocebus aethiops
  • DNA Damage*
  • DNA Replication / drug effects
  • Embryo, Nonmammalian / embryology
  • Embryo, Nonmammalian / metabolism*
  • Erythroid-Specific DNA-Binding Factors / deficiency
  • Erythroid-Specific DNA-Binding Factors / genetics*
  • Erythroid-Specific DNA-Binding Factors / metabolism
  • Flow Cytometry
  • Gene Expression Regulation, Developmental
  • Heterochromatin / metabolism
  • Immunohistochemistry
  • In Situ Hybridization
  • Microscopy, Fluorescence
  • Mutation*
  • Protein Binding
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Two-Hybrid System Techniques
  • Zebrafish / embryology
  • Zebrafish / genetics
  • Zebrafish Proteins / deficiency
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism

Substances

  • Erythroid-Specific DNA-Binding Factors
  • Gon4l protein, zebrafish
  • Heterochromatin
  • Tumor Suppressor Protein p53
  • Zebrafish Proteins
  • Checkpoint Kinase 2
  • Protein Serine-Threonine Kinases
  • Bromodeoxyuridine