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Recombination derived replication in the eukaryotic microbe Leishmania a genome...

Recombination derived replication in the eukaryotic microbe Leishmania a genome wide process? In any organism, the need to reproduce is paramount, with genome replication being the earliest step in the process. The machinery and mechanisms of DNA replication are widely conserved, with initiation occurring at defined bi-dir... ver más

30/09/2019

UNIVERSITY OF GLAS...

183K€

Presupuesto del proyecto: 183K€

Líder del proyecto

UNIVERSITY OF GLASGOW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2019-09-30

MSCA-IF-2016: Individual Fellowships

I+D

Cerrada hace 8 años

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No hay información privada compartida para este proyecto. Habla con el coordinador.

1 Participantes

UNIVERSITY OF GLASGOW

183.45K€ | Lider

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Duración del proyecto: 30 meses Fecha Inicio: 2017-03-06
Fecha Fin: 2019-09-30

Líder del proyecto

UNIVERSITY OF GLASGOW No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 183K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto In any organism, the need to reproduce is paramount, with genome replication being the earliest step in the process. The machinery and mechanisms of DNA replication are widely conserved, with initiation occurring at defined bi-directional DNA synthesis sites termed origins. Though origins may not be conserved DNA sequences, they are defined through binding conserved replication initiator factors. In some circumstances, such as after DNA damage or origin deletion, origin-independent replication can be observed in cellular organisms and can be driven by recombination. However, origin-independent replication is not normally considered to be a genome-wide, central reaction of genome replication. Very recently, genome-wide mapping of DNA replication initiation in two species of the kinetoplastid parasite Leishmania revealed only a single locus-specific origin per chromosome. Analyses of Leishmania S phase length and DNA synthesis speed suggest that a single origin-based strategy is insufficient for complete genome duplication, indicating replication in these eukaryotic microbes relies on origin-independent initiation to support origin-directed initiation. In this proposal, I will test the hypothesis that stochastic origin-independent DNA synthesis initiation events occur throughout the Leishmania genome due to homologous recombination acting on DNA lesions. If correct, this work will reveal the first example of a cellular organism that uses origin-independent replication as a core feature of genome duplication. The genome-wide use of recombination-driven replication would alter our view of DNA replication evolution and would explain the remarkable genome plasticity of Leishmania, with implications for how the parasite adapts genome structure and gene expression in the face of changing environments. Such adaptive change is seen during acquisition of resistance to anti-leishmanial drugs, and so this work will provide insight into the use and development of therapies.

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