The DNA polymerase lambda is required for the repair of non-compatible DNA double strand breaks by NHEJ in mammalian cells.
Nucleic Acids Res
; 34(10): 2998-3007, 2006.
Article
in En
| MEDLINE
| ID: mdl-16738138
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.
Full text:
1
Database:
MEDLINE
Main subject:
Recombination, Genetic
/
DNA Polymerase beta
/
DNA Repair
Limits:
Animals
Language:
En
Year:
2006
Type:
Article