Chromosomal and extrachromosomal DSBs can be induced experimentally in virtually any kind of cell. Such systems led to the dissection of the two major mechanisms of DNA repair: homologous recombination (HR) and non-homologous end-joining (NHEJ). In the lab, fission yeast was used to investigate genetic requirements for microhomology-mediated end- joining (MMEJ), a third DNA repair process poorly characterized so far (Decottignies, 2007).
Image courtesy of Prof. Rosa Aligue Alemany
University of Barcelona, Spain
From yeast to mammals, different studies also reported the insertion of DNA fragments of various sources at experimentally-induced DSBs, including mitochondrial DNA (mtDNA) in budding and fission yeast (Decottignies, 2005), and repetitive DNA in mammalian cells. Interestingly, recent studies reported the association of human genetic diseases with de novo insertions of mtDNA in the nuclear genome, including a patient exposed to Chernobyl radiations. Moreover, systematic sequencing of eukaryotic nuclear genomes revealed the presence of nuclear sequences of mitochondrial origin (NUMTs) in chromosomes, suggesting that capture of mtDNA fragments at naturally occurring DSBs took place during evolution, remodeling the nuclear genome. We are interested in studying the mechanisms involved in the transfer/insertion of mtDNA in the nucleus.