RepTime
Financiado
Molecular control of DNA replication timing in mammalian cells
DNA replication is an essential process ensuring the transmission of genetic information and is highly regulated. Specifically, the DNA replication-timing program ensures that the sites of initiation of DNA replication, termed ori...
DNA replication is an essential process ensuring the transmission of genetic information and is highly regulated. Specifically, the DNA replication-timing program ensures that the sites of initiation of DNA replication, termed origins, are not all activated simultaneously but follow a cell-type specific schedule. This pathway is conserved throughout eukaryotic evolution, however its molecular control and biological role are not fully understood. In this proposal I aim to understand key aspects of replication-timing program by employing a combination of advanced mouse genetics, genomics, cell biology and proteomics. Currently one of the major limitations in the mammalian DNA replication field is the elusive identity of origins. I aim to comprehensively map origins in a variety of mouse cells/tissues and relate the regulation of origin firing to the control of gene expression and three-dimensional nuclear architecture. I have discovered that Rif1 controls replication timing and links it to nuclear three-dimensional organization. I have also revealed the existence of a novel Rif1-independent pathway that controls the timing of a significant fraction of the late-replicating genome, identified by constitutive association with a key nuclear architecture component, Lamin B1. Here, I propose complementary approaches to understand the molecular mechanism by which Rif1 coordinates replication timing and nuclear organization as well as the molecular underpinnings of the novel pathway instructing late-replication in Lamin B1-associated regions. Finally, my goal is to understand the in vivo biological role of the replication-timing program. Our preliminary data identify mammalian X inactivation as a process where replication timing may play a fundamental part. My ultimate objective is to contribute to the realization of a comprehensive understanding of nuclear function, integrating the co-regulation of DNA replication with gene expression, epigenetic inheritance and DNA repair.
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Duración del proyecto: 83 meses
Fecha Inicio: 2017-04-10
Fecha Fin: 2024-03-31
Fecha Fin: 2024-03-31
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2024-03-31
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2016-COG:
ERC Consolidator Grant
Cerrada
hace 8 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
THE UNIVERSITY OF EDINBURGH
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
307.95K€ |
Participante