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The DNA polymerase is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells

Abstract : DNA polymerase lambda (pollambda) is a recently identified DNA polymerase whose cellular function remains elusive. Here we show, that pollambda 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 pollambda (pollambdaDN) decreases the frequency of NHEJ events in response to I-Sce-I-induced DSB whereas inactivated forms of its homologues polbeta and polmu 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, pollambdaDN-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 pollambda 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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Journal articles
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https://www.hal.inserm.fr/inserm-02438660
Contributor : Philippe Pourquier <>
Submitted on : Tuesday, January 14, 2020 - 12:12:13 PM
Last modification on : Wednesday, March 18, 2020 - 1:37:11 AM

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Jean-Pascal Capp, François Boudsocq, Pascale Bertrand, Audrey Laroche-Clary, Philippe Pourquier, et al.. The DNA polymerase is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells. Nucleic Acids Research, Oxford University Press, 2006, 34 (10), pp.2998-3007. ⟨10.1093/nar/gkl380⟩. ⟨inserm-02438660⟩

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