The DNA polymerase lambda is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells.
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.
Capp
Jean-Pascal
JP
Equipe, Instabilité Génétique et Cancer, Institut de Pharmacologie et de Biologie Structurale, UMR CNRS 5089, 205 route de Narbonne, 31077 Toulouse, France.
Boudsocq
François
F
Bertrand
Pascale
P
Laroche-Clary
Audrey
A
Pourquier
Philippe
P
Lopez
Bernard S
BS
Cazaux
Christophe
C
Hoffmann
Jean-Sébastien
JS
Canitrot
Yvan
Y
D000818:Animals; D001483:Base Sequence; D002166:Camptothecin / Q000633:toxicity; D004247:DNA / Q000737:chemistry; D004249:DNA Damage; D019951:DNA Polymerase beta / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004260:DNA Repair; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D015252:Deoxyribonucleases, Type II Site-Specific / Q000378:metabolism; D042822:Genomic Instability; D008969:Molecular Sequence Data; D009154:Mutation; D011839:Radiation, Ionizing; D011995:Recombination, Genetic; D029701:Saccharomyces cerevisiae Proteins
D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; C415367:DNA polymerase beta2; C407743:DNA polymerase mu; D019951:DNA Polymerase beta; D004259:DNA-Directed DNA Polymerase; C037725:SCEI protein, S cerevisiae; D015252:Deoxyribonucleases, Type II Site-Specific; D002166:Camptothecin