Roles and loading mechanisms of SMC complexes in replicative stress response in S. cerevisiae
The three SMC complexes Cohesin, Condensin and SMC5/6 are mainly studied for their role in mitosis, nevertheless they all localize at replication forks in replicative stress conditions. During this thesis, we focused on Cohesin and Condensin. In the first part we describe a new role for the condensin complex in response to replicative stress. In the presence of Hydroxyurea (HU) and Methyl-Methan-Sulfonate (MMS), condensin is required for cell growth and replication fork progression. Moreover, our results show that condensin limits the accumulation of the specific single-strand DNA (ssDNA) binding protein RPA (Replication Protein A) in the vicinity of replication forks under HU treatment, revealing that condensin limits ssDNA accumulation during replicative stress. In this way, Condensin could protect replication fork integrity and genome stability in response to replicative stress. In the second part, we decipher the cohesin recruitment mechanisms at replication fork under replicative stress. In that context, cohesin reinforces sister chromatid cohesion and facilitates homologous recombination (HR) dependent replication fork restart pathways. We show here that the SMC-like MRX complex, the histone methyl transferase Set1 and the histone acetyl transferase Gcn5 are required for cohesin recruitment at stalled replication forks. Our results show that these three proteins affect histone H3 dynamics on replicated DNA in response to replicative stress. Gcn5 and MRX reduce H3 density whereas Set1 maintains nucleosome mobility. These two parameters seem to be important for efficient response to replicative stress and for SMC complexes loading close to stressed replication forks.
Save the date
A Tribute to Angelos Constantinou
du
10/03/2025
jusqu'au 13/03/2025
Village Club de Carry-Le-Rouet, France
