Journal
DNA REPAIR
Volume 7, Issue 5, Pages 725-733Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.dnarep.2008.01.010
Keywords
ionizing radiation (IR); DNA repair; linear energy transfer (LET); non-homologous end-joining (NHEJ); homologous recombination repair; (HRR)
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Ionizing radiation (IR) induced DNA double strand breaks (DSBs) are repaired by both non-homologous end-joining (NHEJ) and homologous recombination repair (HRR) in mammalian cells. The NHEJ repair includes a Ku-dependent main pathway and a PARP-1-dependent complementary pathway. Compared with low linear energy transfer (LET) IR (X or gamma ray) at the same doses, high LET IR (high-charge particles) induces more cell death because of ineffective DNA repair. However, it remains unclear whether high LET IR inhibits all repair or specifically one repair pathway By combining the assays of clonogenic survival, G2M checkpoint and gamma H2AX in the cell lines with deficiencies in different repair genes, we show here that high LET IR inhibits only the Ku-dependent main NHEJ pathway and does not inhibit either the HRR pathway or the PARP-1-dependent complementary NHEJ pathway In addition, by developing an assay to detect small fragments of DSB (< 400bp) and by detecting the binding abilities of purified Ku and PARP to different sized dsDNA, we present a possible link for explaining the phenotypes. When compared with low LET IR at the same dose, high LET IR might induce similar yields of DNA DSBs in total but it might induce more small fragments of DNA DSBs (< 40 base pairs) that prevent Ku binding efficiently to two ends of one DSB fragment at the same time, thus delaying Ku-dependent repair. (c) 2008 Elsevier B.V. All rights reserved.
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