GENECARE
Financiado
GENome and Epigenome integrity Consecutive to DSBs in Active REgion
DNA double-strand breaks (DSBs) are toxic lesions, holding the potential to generate mutations, copy number alterations and translocations. Beyond programmed DSBs induced during meiosis and antibody repertoire generation, DSBs wer...
DNA double-strand breaks (DSBs) are toxic lesions, holding the potential to generate mutations, copy number alterations and translocations. Beyond programmed DSBs induced during meiosis and antibody repertoire generation, DSBs were historically seen as rare, mostly therapy-induced DNA lesions. However, recent work unequivocally revealed that endogenous DSBs occur far more frequently that initially believed, including in physiological conditions, such as neuron stimulation, and mainly fall within transcribed loci, partly due to topoisomerase II activity. Notably, altered repair of these DSBs is not only emerging as a driver of oncogenesis but also of many developmental, neurological and aging-associated diseases.
Our lab has pioneered the discovery of a dedicated pathway that, alike TC-NER for damaged nucleotides, is actually mobilized to repair such DSBs in transcribed loci, coined as Transcription Coupled DSB repair (TC-DSBR). This pathway entails chromatin signaling, nuclear reorganization and the regulation of transcription, but remains poorly characterized overall.
Using advanced genomics, proteomics and microscopy, here we intend to perform an in-depth characterization of the TC-DSBR protein network, of the function of chromatin and nuclear organization in this process, to explore its potential as a target for cancer therapy and to investigate its relevance in maintaining genomic and epigenomic integrity in physiological conditions that trigger DSB in active genes, here in stimulated neurons.
By deciphering the mechanisms that ensure repair of DSBs in transcribed loci, this project holds the potential to expand our knowledge on the biogenesis of translocations and cancer onset, to provide new topoisomerase-poison-based therapeutic strategies but also to provide major breakthroughs in our understanding of neurodegenerative diseases.
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Duración del proyecto: 62 meses
Fecha Inicio: 2021-07-05
Fecha Fin: 2026-09-30
Fecha Fin: 2026-09-30
Línea de financiación: concedida
El organismo H2020 notifico la concesión del proyecto el día 2021-07-05
Línea de financiación objetivo
El proyecto se financió a través de la siguiente ayuda:
ERC-2020-ADG:
ERC ADVANCED GRANT
Cerrada
hace 4 años
Presupuesto
El presupuesto total del proyecto asciende a
2M€
Líder del proyecto
CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE...
No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico
TRL
4-5
Perfil tecnológico
TRL
4-5
412.37K€ |
Participante