Udu deficiency activates DNA damage checkpoint.
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.
Lim
Chiaw-Hwee
CH
Laboratory of Developmental Signalling and Patterning, Genes and Development Division, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673.
Chong
Shang-Wei
SW
Jiang
Yun-Jin
YJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D019521:Body Patterning / Q000235:genetics; D001973:Bromodeoxyuridine / Q000378:metabolism; D019556:COS Cells; D002453:Cell Cycle / Q000235:genetics; D064447:Checkpoint Kinase 2; D002522:Chlorocebus aethiops; D004249:DNA Damage; D004261:DNA Replication / Q000187:drug effects; D004625:Embryo, Nonmammalian / Q000196:embryology / Q000378:metabolism*; D050981:Erythroid-Specific DNA-Binding Factors / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D005434:Flow Cytometry; D018507:Gene Expression Regulation, Developmental; D006570:Heterochromatin / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008856:Microscopy, Fluorescence; D009154:Mutation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques; D015027:Zebrafish / Q000196:embryology / Q000235:genetics; D029961:Zebrafish Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism
D050981:Erythroid-Specific DNA-Binding Factors; C522982:Gon4l protein, zebrafish; D006570:Heterochromatin; D016159:Tumor Suppressor Protein p53; D029961:Zebrafish Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; D001973:Bromodeoxyuridine