Deciphering the molecular mechanisms of the prominent DNA double-strand breaks (DSBs) NHEJ repair pathway in yeast: from short-range to larg

The aim of our project is to decipher the molecular mechanisms underlying the prominent DNA double-strand breaks (DSBs) repair pathway, the NHEJ (non-homologous end joining). DSBs are caused by various sources. When there are no repaired, they can led to cell death, chromosomal aberration or immunodeficiency syndromes. NHEJ starts with DSB recognition by the heterodimeric protein Ku that recruits the processing factors (nucleases, polymerases) and the ligase complex to end with DNA ligation. We are mainly focus on the structural studies of long-range to short-range synaptic transition in S. cerevisiae NHEJ, as a model of study. A major difference is the absence of a yeast DNA-PKcs that forms in human a complex with the Ku protein tethering the broken DNA and preventing their degradation. MRX (MRN in human) has been proposed to fulfil this work in yeast, but this remains to be demonstrated.