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Poly(ADP-ribose) polymerase (PARP-1) is not involved in DNA double-strand break recovery.

Abstract : BACKGROUND: The cytotoxicity and the rejoining of DNA double-strand breaks induced by gamma-rays, H2O2 and neocarzinostatin, were investigated in normal and PARP-1 knockout mouse 3T3 fibroblasts to determine the role of poly(ADP-ribose) polymerase (PARP-1) in DNA double-strand break repair. RESULTS: PARP-1-/- were considerably more sensitive than PARP-1+/+ 3T3s to induced cell kill by gamma-rays and H2O2. However, the two cell lines did not show any significant difference in the susceptibility to neocarzinostatin below 1.5 nM drug. Restoration of PARP-1 expression in PARP-1-/- 3T3s by retroviral transfection of the full PARP-1 cDNA did not induce any change in neocarzinostatin response. Moreover the incidence and the rejoining kinetics of neocarzinostatin-induced DNA double-strand breaks were identical in PARP-1+/+ and PARP-1-/- 3T3s. Poly(ADP-ribose) synthesis following gamma-rays and H2O2 was observed in PARP-1-proficient cells only. In contrast neocarzinostatin, even at supra-lethal concentration, was unable to initiate PARP-1 activation yet it induced H2AX histone phosphorylation in both PARP1+/+ and PARP-1-/- 3T3s as efficiently as gamma-rays and H2O2. CONCLUSIONS: The results show that PARP-1 is not a major determinant of DNA double-strand break recovery with either strand break rejoining or cell survival as an endpoint. Even though both PARP-1 and ATM activation are major determinants of the cell response to gamma-rays and H2O2, data suggest that PARP-1-dependent poly(ADP-ribose) synthesis and ATM-dependent H2AX phosphorylation, are not inter-related in the repair pathway of neocarzinostatin-induced DNA double-strand breaks.
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Submitted on : Wednesday, December 6, 2006 - 2:44:06 PM
Last modification on : Wednesday, October 14, 2020 - 3:45:55 AM
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Georges Noël, Nicole Giocanti, Marie Fernet, Frédérique Mégnin-Chanet, Vincent Favaudon. Poly(ADP-ribose) polymerase (PARP-1) is not involved in DNA double-strand break recovery.. BMC Cell Biology, BioMed Central, 2003, 4, pp.7. ⟨10.1186/1471-2121-4-7⟩. ⟨inserm-00115574⟩

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