Structural and functional analysis of the human Rad50 and Mre11 DNA repair complex : reaching out for flexible solutions

DNA, the genetic material, contains essential information for the proper function of cells. lt is therefore of great importance that the integrity of the genome is carefully maintained during metabolic processes. Special challenges for genome maintenance pathways are DNA ends that arise in cells due to different causes. DNA ends, in the form of telomeres, naturally occur at the termini of the linear eukaryotic chromosomes. Random DNA double-strand breaks (DSBs) can be induced by various exogenous and endogenous DNA darnaging agents. In contrast, the cell can intentionally induce sitespecific DSBs in specialized processes to create genetic diversity during immune system development and meiosis. Impraper processing of these DNA ends imposes a high risk for genetic rearrangements that can lead to cell death, cell maltunetion or carcinogenesis. Therefore, it is of great importance that the DNA ends are processed and/or repaired accurately. For this purpose several mechanisms exist that depend on specific specialized protein machineries. The DSB repair pathway used depends on the circumstances under which the break occurs. One protein complex that is involved in multiple genome maintenance pathways that deal with DNA ends consists of three proteins: Rad50, Mre11 and Nbs1. The aim of this thesis is to ga in insights in the role of this Rad50 protein complex in DNA end metabolism