Cleavage of BLM and sensitivity of Bloom's syndrome cells to hydroxurea and UV-C radiation.
Patients with Bloom's syndrome (BS) show a strong genetic instability and a predisposition to all types of cancer. Here, we report that the Bloom's syndrome protein (BLM) is cleaved in response to hydroxyurea (HU)- or UVC-induced apoptosis. The appearance and solubility of BLM proteolytic products differed according to whether proteolysis occurred in response to HU or UVC. One BS cell line homozygous for a null mutation in BLM was resistant to both UVC- and HU-induced apoptosis, while another one expressing a mutated BLM protein was resistant to HU-induced apoptosis but displayed normal sensitivity to UVC. Thus, UVC and HU appear to induce apoptosis through distinct pathways.
Ababou
Mouna
M
Centre National de la Recherche Scientifique, Unité Mixte de Recherche 1598, Institut Gustave Roussy, 39 Rue Camille Desmoulins, 94 805 Villejuif Cedex, France.
Dumaire
Virginie
V
Lécluse
Yann
Y
Amor-Guéret
Mounira
M
D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D001816:Bloom Syndrome / Q000188:drug therapy* / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D004265:DNA Helicases / Q000737:chemistry / Q000378:metabolism*; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology*; D007150:Immunohistochemistry; D020014:K562 Cells; D053484:RecQ Helicases; D013997:Time Factors; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D000251:Adenosine Triphosphatases; C097151:Bloom syndrome protein; D004265:DNA Helicases; D053484:RecQ Helicases; D006918:Hydroxyurea