Published online 31 May 2006
© 2006 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-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.
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The DNA polymerase 
is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells
Equipe, ‘Instabilité Génétique et Cancer’, Institut de Pharmacologie et de Biologie Structurale UMR CNRS 5089, 205 route de Narbonne, 31077 Toulouse, France 1 Département de Radiobiologie et Radiopathologie 60-68 avenue Général Leclerc, UMR 217 CNRS-CEA, 92265 Fontenay aux Roses cedex, France 2 Institut Bergonié INSERM E437, 229 cours de l'Argonne, 33076 Bordeaux, France
*To whom correspondence should be addressed: Tel: +33 5 61 17 5861; Fax: +33 5 61 17 5994; Email: Yvan.Canitrot{at}ipbs.fr
*Correspondence may also be addressed to Jean-Sébastien Hoffmann. Tel: +33 5 61 17 59 75; Fax: +33 5 61 17 59 94; Email: jseb{at}ipbs.fr
Received March 27, 2006. Revised April 28, 2006. Accepted May 2, 2006.
DNA polymerase lambda (pol
) is a recently identified DNA polymerase whose cellular function remains elusive. Here we show, that pol participates at the molecular level in a chromosomal context, in the repair of DNA double strand breaks (DSB) via non-homologous end joining (NHEJ) in mammalian cells. The expression of a catalytically inactive form of pol (polDN) decreases the frequency of NHEJ events in response to I-Sce-I-induced DSB whereas inactivated forms of its homologues polß and polµ do not. Only events requiring DNA end processing before ligation are affected; this defect is associated with large deletions arising in the vicinity of the induced DSB. Furthermore, polDN-expressing cells exhibit increased sensitization and genomic instability in response to ionizing radiation similar to that of NHEJ-defective cells. Our data support a requirement for pol in repairing a subset of DSB in genomic DNA, thereby contributing to the maintenance of genetic stability mediated by the NHEJ pathway.
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