Fission yeast NUMTs are preferentially located in intergenic regions associated with replication origins

NUMTs are fragments of mtDNA that escaped from mitochondria to get inserted into nuclear DNA. NUMTs are present in almost all eukaryotic genomes sequenced so far and it has been proposed that our genome is being continuously colonized by mtDNA. This phenomenon is threatening genome stability and several human diseases have been associated with de novo insertions of mtDNA into nuclear genes. MtDNA insertions probably occur during nuclear DNA double-strand break repair and rely on NHEJ machinery. To get more insight into the mechanisms of NUMT insertion, a genome-wide analysis of NUMT insertion sites was carried out in S. pombe. Unlike budding yeast, fission yeast does not present marks of NUMT duplication events. Intriguingly, NUMTs are completely absent from chromosome III, possibly reflecting the ancient acquisition of this chromosome from another fission yeast species. The analysis revealed a preferential localisation of NUMTs in intergenic regions of chromosomes I and II, with no preference for promoters, unlike LTR retrotransposons. When inserted into promoters, NUMTs did not affect gene transcription level. Interestingly, intergenic NUMTs were found to be preferentially associated with previously described ORC1/MCM6 binding sites. Data will be presented about the relationship between NUMTs and DNA replication origins unravelled in this study.