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Replisome Proximal Protein Associations and Dynamic Proteomic Changes at Stalled Replication Forks.
Jurkovic, Carla-Marie; Raisch, Jennifer; Tran, Stephanie; Nguyen, Hoang Dong; Lévesque, Dominique; Scott, Michelle S; Campos, Eric I; Boisvert, François-Michel.
Afiliação
  • Jurkovic CM; Faculty of Medicine and Health Sciences, Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, Québec, Canada.
  • Raisch J; Faculty of Medicine and Health Sciences, Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, Québec, Canada.
  • Tran S; Genetics & Genome Biology Program, Department of Molecular Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
  • Nguyen HD; Faculty of Medicine and Health Sciences, Department of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Québec, Canada.
  • Lévesque D; Faculty of Medicine and Health Sciences, Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, Québec, Canada.
  • Scott MS; Faculty of Medicine and Health Sciences, Department of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, Québec, Canada.
  • Campos EI; Genetics & Genome Biology Program, Department of Molecular Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. Electronic address: eric.campos@sickkids.ca.
  • Boisvert FM; Faculty of Medicine and Health Sciences, Department of Immunology and Cell Biology, Université de Sherbrooke, Sherbrooke, Québec, Canada. Electronic address: fm.boisvert@usherbrooke.ca.
Mol Cell Proteomics ; 23(5): 100767, 2024 May.
Article em En | MEDLINE | ID: mdl-38615877
ABSTRACT
DNA replication is a fundamental cellular process that ensures the transfer of genetic information during cell division. Genome duplication takes place in S phase and requires a dynamic and highly coordinated recruitment of multiple proteins at replication forks. Various genotoxic stressors lead to fork instability and collapse, hence the need for DNA repair pathways. By identifying the multitude of protein interactions implicated in those events, we can better grasp the complex and dynamic molecular mechanisms that facilitate DNA replication and repair. Proximity-dependent biotin identification was used to identify associations with 17 proteins within four core replication components, namely the CDC45/MCM2-7/GINS helicase that unwinds DNA, the DNA polymerases, replication protein A subunits, and histone chaperones needed to disassemble and reassemble chromatin. We further investigated the impact of genotoxic stress on these interactions. This analysis revealed a vast proximity association network with 108 nuclear proteins further modulated in the presence of hydroxyurea; 45 being enriched and 63 depleted. Interestingly, hydroxyurea treatment also caused a redistribution of associations with 11 interactors, meaning that the replisome is dynamically reorganized when stressed. The analysis identified several poorly characterized proteins, thereby uncovering new putative players in the cellular response to DNA replication arrest. It also provides a new comprehensive proteomic framework to understand how cells respond to obstacles during DNA replication.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteômica / Replicação do DNA / Hidroxiureia Limite: Humans Idioma: En Revista: Mol Cell Proteomics Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Canadá

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteômica / Replicação do DNA / Hidroxiureia Limite: Humans Idioma: En Revista: Mol Cell Proteomics Assunto da revista: BIOLOGIA MOLECULAR / BIOQUIMICA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Canadá