Resolution of complex ends by Nonhomologous end joining - better to be lucky than good?

The Nonhomologous end joining pathway is essential for efficient repair of chromosome double strand breaks. This pathway consequently plays a key role in cellular resistance to break-inducing exogenous agents, as well as in the developmentally-programmed recombinations that are required for adaptive immunity. Chromosome breaks often have complex or "dirty" end structures that can interfere with the critical ligation step in this pathway; we review here how Nonhomologous end joining resolves such breaks.