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

doi:10.1186/1471-2121-4-7

BMC Cell Biology
Volume 4

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Mégnin-Chanet F
Favaudon V

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Research article

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

Georges Noël¹^,2 , Nicole Giocanti¹ , Marie Fernet¹^,3 , Frédérique Mégnin-Chanet¹ and Vincent Favaudon¹

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

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

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

author email corresponding author email

BMC Cell Biology 2003, 4:7doi: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, H₂O₂and 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 H₂O₂was 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.