Ku-Mediated Coupling of DNA Cleavage and Repair during Programmed Genome Rearrangements in the Ciliate

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DNA double-strand breaks (DSBs) are potential threats for chromosome stability, but they are usually repaired by two major pathways, homologous recombination or non-homologous end joining (NHEJ). DSBs can also be essential during physiological processes, such as the programmed removal of germline sequences that takes place in various eukaryotes, including ciliates, during somatic differentiation. We use the ciliate Paramecium tetraurelia as a unicellular model to study how DNA breakage and DSB repair are coordinated during programmed genome rearrangements. In this organism, assembly of the somatic genome involves the elimination of ∼25% of germline DNA, including the precise excision of thousands of short Internal Eliminated Sequences (IES) scattered along germline chromosomes. A domesticated piggyBac transposase, PiggyMac, is required for double-strand DNA cleavage at IES ends and IES excision sites are very precisely repaired by the NHEJ pathway. Here, we report that a specialized Ku heterodimer, specifically expressed during programmed genome rearrangements, is an essential partner of PiggyMac and activates DNA cleavage. We propose that incorporation of DSB repair proteins in a pre-cleavage complex constitutes a safe and efficient way for Paramecium to direct thousands of programmed DSBs to the NHEJ pathway and make sure that somatic chromosomes are assembled correctly.

Vyšlo v časopise: Ku-Mediated Coupling of DNA Cleavage and Repair during Programmed Genome Rearrangements in the Ciliate. PLoS Genet 10(8): e32767. doi:10.1371/journal.pgen.1004552
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004552

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