Disruption of B-myb in DT40 cells reveals novel function for B-Myb in the response to DNA-damage.
B-Myb is a highly conserved vertebrate member of the Myb transcription factor family, which is expressed in virtually all proliferating cells. A large body of evidence suggests that B-Myb plays an important role in cell cycle regulation; however, the exact nature of its function has not yet been clarified. We have used gene targeting in chicken DT40 cells, a cell line exhibiting very high rates of homologous recombination, to create cells expressing endogenous B-myb in a doxycyclin-dependent manner. We find that the cells proliferate well in the absence of B-Myb, suggesting that B-Myb is not essential for cell proliferation per se. However, cells lacking B-Myb are more sensitive to DNA-damage induced by UV-irradiation and alkylation. Our work provides the first direct evidence for a novel function of B-Myb in the response to DNA-damage. The cells described here should be a useful model to characterize this function in more detail.
Ahlbory
Dörthe
D
Institute for Biochemistry, Westfälische-Wilhelms-Universität Münster, Wilhelm-Klemm-Str. 2, Münster D-48149, Germany.
Appl
Hartmut
H
Lang
Detlef
D
Klempnauer
Karl-Heinz
KH
D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002645:Chickens / Q000235:genetics*; D002999:Clone Cells; D004249:DNA Damage; D004318:Doxycycline / Q000494:pharmacology; D005786:Gene Expression Regulation; D018390:Gene Targeting; D020570:Genes, myb; D005818:Genetic Engineering; D046228:Microarray Analysis; D011401:Promoter Regions, Genetic; D020598:Proto-Oncogene Proteins c-myb / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011995:Recombination, Genetic; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
D020598:Proto-Oncogene Proteins c-myb; D012333:RNA, Messenger; D014157:Transcription Factors; D004318:Doxycycline