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Open Access Highly Accessed Research article

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

Georges Noël12, Nicole Giocanti1, Marie Fernet13, Frédérique Mégnin-Chanet1 and Vincent Favaudon1*

Author Affiliations

1 Unité 350 INSERM, Institut Curie-Recherche, Bâts. 110-112, Centre Universitaire, 91405 Orsay Cedex, France

2 Centre de Protonthérapie d'Orsay, Bât. 101, Centre Universitaire, BP 65, 91402 Orsay Cedex, France

3 Present address: DNA Repair Group, International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon Cedex 08, France

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BMC Cell Biology 2003, 4:7  doi:10.1186/1471-2121-4-7

Published: 16 July 2003

Abstract

Background

The cytotoxicity and the rejoining of DNA double-strand breaks induced by γ-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 γ-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 γ-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 γ-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 γ-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.