Skip Navigation


Nucleic Acids Research Advance Access originally published online on July 4, 2008
Nucleic Acids Research 2008 36(13):4454-4464; doi:10.1093/nar/gkn403
This Article
Right arrow Full Text Freely available
Right arrow Print PDF (7390K) Freely available
Right arrow Screen PDF (790K) Freely available
Right arrowOA All Versions of this Article:
36/13/4454    most recent
gkn403v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Godon, C.
Right arrow Articles by Favaudon, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Godon, C.
Right arrow Articles by Favaudon, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2008, Vol. 36, No. 13 4454-4464
© 2008 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

PARP inhibition versus PARP-1 silencing: different outcomes in terms of single-strand break repair and radiation susceptibility

Camille Godon1,2, Fabrice P. Cordelières1,3,4, Denis Biard5, Nicole Giocanti1,2, Frédérique Mégnin-Chanet1,2, Janet Hall1,2 and Vincent Favaudon1,2,*

1Institut Curie, Centre de Recherche 2Inserm, U612, 3CNRS, UMR146, 4Plateforme d’Imagerie Cellulaire et Tissulaire, Institut Curie, Bât. 110-112, Centre Universitaire, F-91405 Orsay and 5Commissariat à l'Energie Atomique, CEA-DSV-IRCM, Inserm U602, Hôpital Paul Brousse, Bât. Lavoisier, 12-16 avenue Paul Vaillant Couturier, 94807 Villejuif Cedex, France

*To whom correspondence should be addressed. Tel: +33 169 86 3188; Fax: +33 169 86 3187; Email: vincent.favaudon{at}curie.fr

Received March 14, 2008. Revised June 5, 2008. Accepted June 9, 2008.

The consequences of PARP-1 disruption or inhibition on DNA single-strand break repair (SSBR) and radio-induced lethality were determined in synchronized, isogenic HeLa cells stably silenced or not for poly(ADP-ribose) polymerase-1 (PARP-1) (PARP-1KD) or XRCC1 (XRCC1KD). PARP-1 inhibition prevented XRCC1-YFP recruitment at sites of 405 nm laser micro irradiation, slowed SSBR 10-fold and triggered the accumulation of large persistent foci of GFP-PARP-1 and GFP-PCNA at photo damaged sites. These aggregates are presumed to hinder the recruitment of other effectors of the base excision repair (BER) pathway. PARP-1 silencing also prevented XRCC1-YFP recruitment but did not lengthen the lifetime of GFP-PCNA foci. Moreover, PARP-1KD and XRCC1KD cells in S phase completed SSBR as rapidly as controls, while SSBR was delayed in G1. Taken together, the data demonstrate that a PARP-1- and XRCC1-independent SSBR pathway operates when the short patch repair branch of the BER is deficient. Long patch repair is the likely mechanism, as GFP-PCNA recruitment at photo-damaged sites was normal in PARP-1KD cells. PARP-1 silencing elicited hyper-radiosensitivity, while radiosensitization by a PARP inhibitor reportedly occurs only in those cells treated in S phase. PARP-1 inhibition and deletion thus have different outcomes in terms of SSBR and radiosensitivity.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Biol. Reprod.Home page
M. L. Meyer-Ficca, J. Lonchar, C. Credidio, M. Ihara, Y. Li, Z.-Q. Wang, and R. G. Meyer
Disruption of Poly(ADP-Ribose) Homeostasis Affects Spermiogenesis and Sperm Chromatin Integrity in Mice
Biol Reprod, July 1, 2009; 81(1): 46 - 55.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
D. Sagan, R. Muller, C. Kroger, A. Hematulin, S. Mortl, and F. Eckardt-Schupp
The DNA repair protein NBS1 influences the base excision repair pathway
Carcinogenesis, March 1, 2009; 30(3): 408 - 415.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.