Induction of postmeiotic DNA double-strand breaks by the Pnu1 endonuclease in Schizosaccharomyces pombe.

Abstract

Meiosis is a source of genetic variation in eukaryotes. Meiosis in the eukaryotic fission yeast Schizosaccharomyces pombe leads to the formation of spores that are particularly resistant to environmental stresses. In addition to external factors, internal processes may nevertheless contribute to cellular stress and impact the genome. This study investigates the role of Pnu1 as the major meiotic nuclease in S. pombe. Transcription and cellular expression of Pnu1 are regulated upon specific phases of meiosis, while its mitochondrial localization is also altered during this process. As a result, Pnu1 induces fragmentation of both genomic and mitochondrial DNA in the postmeiotic phase. This sugar-nonspecific endonuclease generates random double-strand breaks across the genome, an activity that appears to be mediated by direct interaction with chromatin. Given the high spore viability (∼95%) and the widespread occurrence of this phenomenon, this fragmentation appears to be physiological rather than apoptotic as observed in mammals. EndoG is the mammalian homologue of Pnu1 and is a caspase-independent apoptotic endonuclease that can allow cell survival. This study further describes the dynamics of Pnu1 action and supports the conclusion that Pnu1 is a major meiotic endonuclease of S. pombe responsible for a transient postmeiotic fragmentation of cellular DNA, potentially contributing to genetic variability.