Single-molecule approaches to unravel the mechanism of SMC proteins

Abstract

Every cell deals with the challenge of organising its DNA. First, the DNA needs to be compacted in size by several orders of magnitude. For example, in each human cell, 2 meters of DNA need to fit inside a micron-sized cell nucleus. Second, the DNA needs to stay accessible for cellular processes such as transcription and replication. To achieve these goals, cells are assisted by proteins that organise the DNA by locally bending the DNA, wrapping DNA around them, or by making DNA loops. A prime example are the Structural Maintenance of Chromosomes (SMC) family of proteins,which is known to be essential for DNA organisation. In eukaryotes, the SMC complex cohesin is responsible for keeping sister-chromatids together until the cell is ready to divide. Without cohesin, division might occur prematurely, leading to unevenly divided DNA. The SMC complex condensin is responsible for compacting the DNA into mitotic chromosomes. Indeed, without condensin, the DNA does not formproperly organised chromosomes. This thesis describes a series of experiments that aim to understand the molecular mechanism of these SMC proteins.