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LoopSMC

Financiado

Mechanism, Regulation and Functions of DNA Loop Extrusion by SMC complexes

Life and evolution of organisms relies on the maintenance, integration, propagation, and readout of genetic information. This information is stored in chromosomes that have a specific three-dimensional structure, a condensed yet a... ver más

31/03/2028

MPG

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

MAXPLANCKGESELLSCHAFT ZUR FORDERUNG DER WISSE... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Ver 1 Participantes

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-12-20

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2022-STG: ERC STARTING GRANTS

I+D

Cerrada hace 2 años

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1 Participantes

MPG

1.50M€ | Lider

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Duración del proyecto: 63 meses Fecha Inicio: 2022-12-20
Fecha Fin: 2028-03-31

Presupuesto del proyecto 2M€

Descripción del proyecto Life and evolution of organisms relies on the maintenance, integration, propagation, and readout of genetic information. This information is stored in chromosomes that have a specific three-dimensional structure, a condensed yet accessible form of DNA that is dynamically folded during the lifespan of cells. How DNA is folded within chromosomes has however remained a mystery. It has been proposed that this is achieved by a process of loop extrusion in which SMC (Structural Maintenance of Chromosomes) complexes that are multi-subunit ATPases present in all kingdoms of life – including condensin and cohesin – reel DNA into loops, thereby organizing genomic DNA into higher-order structures. Recent in vitro single-molecule studies, stimulated by our initial discovery on condensin, provided direct evidences that both condensin and cohesin can indeed generate chromatin loops by extrusion. However, the most fundamental questions relating to this process remain unanswered: What is the molecular mechanism of loop extrusion? How is this process regulated? What are the functional roles of SMC-mediated loop extrusion beyond condensation? To address these questions, we will synergistically combine our single-molecule loop extrusion assay with correlative light and electron tomography and force spectroscopy to reveal both dynamic and structural aspects of loop extrusion and SMC proteins. Specifically, we will resolve how SMC complexes function as molecular ‘motors’, how regulatory factors modulate the kinetics of loop extrusion, and how loop extrusion impacts cellular functions like chromosome segregation and gene recombination, all at the single molecule level. In the long term, our findings will provide vital insights into the basic packaging structure of the genome which directly governs its biological function.

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