Recruitment of RMM proteins to the chromosomal axis during meiosis

Details

Supervisors

Claeys Bouuaert, Corentin

Faculty

Faculté des sciences

Degree label

Master [120] en biochimie et biologie moléculaire et cellulaire, à finalité approfondie

Abstract

Meiosis is a fundamental process for generating genetic diversity in eukaryotic species. During the initial stages of this process, particularly in prophase I, a key mechanism known as homologous recombination takes place. This mechanism facilitates the exchange of genetic material between homologous chromosomes through the formation of crossovers. In Saccharomyces cerevisiae, homologous recombination is initiated by the formation of double-strand breaks (DSBs) in DNA, a process catalysed by the protein Spo11, an endonuclease derived from topoisomerase IV. Spo11 serves as the catalytic unit strictly responsible for inducing these breaks, but nine other proteins are also required to enable this operation. These ten proteins are organized into three distinct sub-complexes: the core complex, composed of Spo11, Ski8, Rec102, and Rec104; the MRX complex, consisting of Mre11, Rad50, and Xrs2; and the RMM complex, composed of Rec114, Mei4, and Mer2. Additionally, other proteins, particularly those constituting the chromosomal protein axis, play a crucial role in the initiation of these breaks. Indeed, during recombination, DNA adopts a specific conformation of successive loops anchored to an axial protein structure, primarily formed by the proteins Hop1, Red1, and Red8. In this thesis, we will focus on the study of interactions among the proteins of the RMM complex. Previous studies have shown that these proteins are the first to localize to chromosomes, forming condensates that serve as platforms for the anchoring and activity of other proteins involved in DSB formation. In the laboratory, it has been demonstrated that Rec114 and Mei4 interact to form a complex. However, interactions involving Mer2 remain poorly understood. Therefore, we will investigate the role of Mer2 in the formation of these condensates. Early research on Mer2 has revealed that this protein appears to play a central role in the condensation of the RMM complex through various interactions with other proteins as well as with DNA. The interactions of Mer2 with DNA have recently been demonstrated in the laboratory. Here, we will explore the protein interactions of Mer2 with Rec114 as well as with a chromosomal axis protein, Hop1, to better understand how Mer2 facilitates the condensation of the RMM complex proteins.