Tails and cuts: the role of histone post-translational modifications in the formation of programmed double-strand breaks

In eukaryotic organisms, various DNA recombination mechanisms have been described that are an integral part of nuclear differentiation processes. In several places, the recombination is initiated by one or more double-strand breaks that result from the action of specific endonucleolytic activities. The importance of chromatin in controlling susceptibility of DNA to various DNA transactions has been recognized for long. Recent literature links post-transcriptional modifications of the amino-terminal part of histones (the tails) to the formation of developmentally regulated DNA double-strand break (the cuts). In this review, I compare the existing data in three different DNA rearrangement-based processes, i.e., genetic recombination associated to meiosis, lymphoid-specific V(D)J recombination and excision of DNA fragments in the nucleus of ciliates. Inspired by some of the concepts established in the field of transcription, models are proposed for molecular mechanisms that sustain the epigenetic control of programmed double-strand break formation.