Radiation-hypersensitive cancer patients do not manifest protein expression abnormalities in components of the nonhomologous end-joining (NHEJ) pathway

SnapShot: Nonhomologous DNA End Joining (NHEJ)

Cisplatin sensitizes cancer cells to ionizing radiation via inhibition of nonhomologous end joining.

The combination of cisplatin and ionizing radiation (IR) treatment represents a common modality for treating a variety of cancers. These two agents provide considerable synergy during treatment, although the mechanism of this synergy remains largely undefined. We have investigated the mechanism of cisplatin sensitization to IR using a combination of in vitro and in vivo experiments. A clear syn...

The role of nonhomologous end-joining components in telomere metabolism in Kluyveromyces lactis.

The relationship between telomeres and nonhomologous end-joining (NHEJ) is paradoxical, as NHEJ proteins are part of the telomere cap, which serves to differentiate telomeres from DNA double-strand breaks. We explored these contradictory functions for NHEJ proteins by investigating their role in Kluyveromyces lactis telomere metabolism. The ter1-4LBsr allele of the TER1 gene resulted in the int...

Bacterial nonhomologous end joining requires teamwork.

All living organisms must repair DNA double-stranded breaks (DSBs) in order to survive. Many bacteria rely on nonhomologous end joining (NHEJ) when only a single copy of the genome is available and maintain NHEJ pathways with a minimum of two proteins. In this issue, Bhattarai and colleagues identify additional factors that can work together to aid in survival of stationary-phase cells with chr...

Yeast Tdp1 regulates the fidelity of nonhomologous end joining.

Tyrosyl-DNA-phosphodiesterase 1 (Tdp1) can disjoin peptides covalently bound to DNA. We assessed the role of Tdp1 in nonhomologous end joining (NHEJ) and found that linear DNA molecules with 5' extensions showed a high frequency of misrepair in Deltatdp1 cells. The joining errors in Deltatdp1 cells were predominantly 2-4 nucleotide insertions. Ends with 3' extensions or blunt ends did not show ...