Differential regulation of human RecQ family helicases in cell transformation and cell cycle.
Three human RecQ DNA helicases, WRN, BLM and RTS, are involved in the genetic disorders associated with genomic instability and a high incidence of cancer. RecQL1 and RecQL5 also belong to the human RecQ helicase family, but their correlation with genetic disorders, if any, is unknown. We report here that in human B cells transformed by Epstein-Barr virus (EBV), human fibroblasts and umbilical endothelial cells transformed by simian virus 40, the expression of WRN, BLM, RTS and RecQL1 was sharply up-regulated. In B cells this expression was stimulated within 5-40 h by the tumor promoting agent phorbol myristic acetate (PMA). Interestingly, RecQL5beta, an alternative splicing product of RecQL5 with a nuclear localization signal, is expressed in resting B cells without significant modulation of its synthesis by EBV or PMA, suggesting it has a role in resting cells. We also roughly determined the number of copies per cell for the five RecQ helicase in B cells. In addition, levels of the different RecQ helicases are modulated in different ways during the cell cycle of actively proliferating fibroblasts and umbilical endothelial cells. Our results support the view that the levels of WRN, BLM, RTS and RecQL1 are differentially up-regulated to guarantee genomic stability in cells that are transformed or actively proliferating.
Kawabe
T
T
AGENE Research Institute, Kamakura, Kanagawa, Japan.
Tsuyama
N
N
Kitao
S
S
Nishikawa
K
K
Shimamoto
A
A
Shiratori
M
M
Matsumoto
T
T
Anno
K
K
Sato
T
T
Mitsui
Y
Y
Seki
M
M
Enomoto
T
T
Goto
M
M
Ellis
N A
NA
Ide
T
T
Furuichi
Y
Y
Sugimoto
M
M
D000251:Adenosine Triphosphatases / Q000096:biosynthesis* / Q000235:genetics; D017398:Alternative Splicing; D001402:B-Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000821:virology; D002453:Cell Cycle / Q000502:physiology*; D002455:Cell Division; D002461:Cell Line, Transformed / Q000201:enzymology; D002472:Cell Transformation, Viral / Q000235:genetics*; D004265:DNA Helicases / Q000096:biosynthesis* / Q000172:deficiency / Q000235:genetics; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology; D004790:Enzyme Induction; D005090:Exodeoxyribonucleases; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000502:physiology; D006801:Humans; D053484:RecQ Helicases; D013539:Simian virus 40 / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D014898:Werner Syndrome / Q000097:blood / Q000201:enzymology* / Q000235:genetics; D000071657:Werner Syndrome Helicase
D005090:Exodeoxyribonucleases; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; C506731:RECQL4 protein, human; D004265:DNA Helicases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase; D013755:Tetradecanoylphorbol Acetate