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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
The alternative end-joining pathway for repair of DNA double-strand breaks requires PARP1 but is not dependent upon microhomologies
Nucleic Acids Research, Volume 38, No. 18, Article gkq387, Year 2010
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Description
Non-homologous end-joining (NHEJ), the major repair pathway for DNA double-strand breaks (DSB) in mammalian cells, employs a repertoire of core proteins, the recruitment of which to DSB-ends is Ku-dependent. Lack of either of the core components invariably leads to a repair deficiency. There has been evidence that an alternative end-joining operates in the absence of the core components. We used chromosomal reporter substrates to specifically monitor NHEJ of single I-SceI-induced-DSB for detailed comparison of classical and alternative end-joining. We show that rapid repair of both compatible and non-compatible ends require Ku-protein. In the absence of Ku, cells use a slow but efficient repair mode which experiences increasing sequence-loss with time after DSB induction. Chemical inhibition and PARP1-depletion demonstrated that the alternative end-joining in vivo is completely dependent upon functional PARP1. Furthermore, we show that the requirement for PARP1 depends on the absence of Ku but not on DNA-dependent protein kinase (DNA-PKcs). Extensive sequencing of repair junctions revealed that the alternative rejoining does not require long microhomologies. Together, we show that mammalian cells need Ku for rapid and conservative NHEJ. PARP1-dependent alternative route may partially rescue the deficient repair phenotype presumably at the expense of an enhanced mutation rate. © The Author(s) 2010. Published by Oxford University Press.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2952854/bin/supp_38_18_6065__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC2952854/bin/supp_gkq387_Mansour_SuppleFig_revised.ppt
Authors & Co-Authors
Mansour, Wael Yassin
Germany, Hamburg
Medizinischen Fakultät
Egypt, Giza
Cairo University
Rhein, Tim
Germany, Hamburg
Medizinischen Fakultät
Dahm-Daphi, Jochen
Germany, Hamburg
Medizinischen Fakultät
Statistics
Citations: 191
Authors: 3
Affiliations: 2
Identifiers
Doi:
10.1093/nar/gkq387
ISSN:
03051048
e-ISSN:
13624962
Research Areas
Cancer
Genetics And Genomics