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The Role of cohEsin dynamicS at sTAlled ReplicaTion forks

Cohesin, an evolutionary conserved ring-shaped protein complex that topologically entraps DNA, has crucial roles in many structural and functional aspects of chromosomes including sister chromatid cohesion, genome organization, ge... ver más

31/10/2025

USAL

181K€

Presupuesto del proyecto: 181K€

Líder del proyecto

UNIVERSIDAD DE SALAMANCA No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 1149

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2023-05-03

HORIZON-MSCA-2022-PF-01-01: MSCA Postdoctoral Fellowships 2022 ExpectedOutcome:

I+D

Cerrada hace 2 años

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1 Participantes

USAL

181.15K€ | Lider

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Duración del proyecto: 29 meses Fecha Inicio: 2023-05-03
Fecha Fin: 2025-10-31

Líder del proyecto

UNIVERSIDAD DE SALAMANCA No se ha especificado una descripción o un objeto social para esta compañía.

Total investigadores 1149

Presupuesto del proyecto 181K€

Descripción del proyecto Cohesin, an evolutionary conserved ring-shaped protein complex that topologically entraps DNA, has crucial roles in many structural and functional aspects of chromosomes including sister chromatid cohesion, genome organization, gene transcription and DNA repair. The importance of cohesin in the maintenance of genomic stability has been known for some time. Cohesin facilitates double strand breaks repair by homologous recombination and promotes the restart of stalled replication forks by template switching, an error-free DNA tolerance pathway. However, the precise role of cohesin in DNA damage and in the recovery after replication stress is still unknown. Whether cohesin acts exclusively providing close proximity of sister chromatids or its functions exceed simple embracing of DNA has yet to be discerned. Cohesin has been shown to be ubiquitylated upon replication fork arrest. This post-translational modification has been proposed to favour cohesin mobilization and subsequent association with nascent DNA behind the fork. However, the extent to what cohesin dynamics are important in the recovery after replication stress is still to be understood. By a range of multidisciplinary approaches, from biochemistry and enzymology, yeast genetics and molecular biology techniques to high throughput proteomics and bioinformatics analysis of mass spectrometry data, we will gain valuable insight about the interplay between sister chromatid cohesion and DNA damage tolerance and their contribution to successful replication. This basic knowledge about the mechanisms involved in DNA damage responses has demonstrated to be essential in the design of successful strategies against cancer. Remarkably, cohesin is one of the protein complexes most frequently mutated in cancer. This project aims to provide valuable insight about how cohesin mutations cause tumorigenesis.

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