The cellular control enzyme polyADP ribosyl transferase is eliminated in cultured Fanconi anemia fibroblasts at confluency.
Fanconi anemia (FA) is a hereditary disease of unknown pathogenic mechanisms, although mutations in seven different genes can be causative. Six of these genes have been cloned and sequenced. Only slight homology to the DNA of any other known gene has been found with the exception of FANCG which is identical to XRCC9. The function of these genes, including XRCC9, is presently unknown. Since pADP ribosyl transferase (pADPRT) plays a role in apoptosis, and apoptosis is affected in FA cells, we studied the correlation between pADPRT and FA cells. We reinvestigated the previously reported lack of pADPRT activity in fibroblasts from patients with Fanconi anemia. Here we describe the role of the lower redox potential of FA cells and demonstrate that this is an efficient strategy in the prevention of cell death due to the lack of energy under oxidative stress. This strategy is advantageous for the cells under the nonreplicative condition of confluency in which the risk of mutation is low and the prevention of apoptosis permits cell survival. pADPRT is not diminished to the same extent in all complementation groups of FA. It is prominent in FANCA, FANCG and FANCF cells, indicating that these genes control pADPRT diminution. Our experiments suggest that the pADPRT level is linked with the oxidoreduction reactions seen in FA.
Ramirez
Maria Helena
MH
Institut für Biochemie, Freie Universität Berlin, Thielallee 63, D-14195 Berlin, Germany.
Adelfalk
Caroline
C
Kontou
Maria
M
Hirsch-Kauffmann
Monica
M
Schweiger
Manfred
M
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis; D015153:Blotting, Western; D002470:Cell Survival / Q000502:physiology; D002478:Cells, Cultured; D004229:Dithiothreitol / Q000494:pharmacology; D005199:Fanconi Anemia / Q000201:enzymology*; D005347:Fibroblasts; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis* / Q000235:genetics; D013347:Subcellular Fractions / Q000378:metabolism; D013439:Sulfhydryl Reagents / Q000494:pharmacology
D000903:Antibiotics, Antineoplastic; D013439:Sulfhydryl Reagents; D016685:Mitomycin; D011065:Poly(ADP-ribose) Polymerases; D004229:Dithiothreitol