Enlentecer la replicación para completarla: La polimerasa especializada iota (Pol ?) mantiene la estabilidad genómica previniendo la replicación excesiva de ADN por PrimPol

DNA replication is a key event for life as well as the trigger for diseases such as cancer. Failed or incomplete replication can generate genomic instability, an event that precedes genomic rearrangements that promote carcinogenesis. The success of the replication process depends on the correct exec...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autor principal: Venerus Arbilla, Sofía
Otros Autores: Mansilla, Sabrina Florencia
Formato: Tesis doctoral acceptedVersion
Lenguaje:Español
Publicado: Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica 2024
Materias:
Pol ?
PrimPol
Tolerancia al ADN dañado
Síntesis por translesión
Recebado
Inversión de horquillas
Replicación del ADN
Estrés replicativo
Chequeo de fase S
Inestabilidad genómica
DNA damage tolerance
Translesion synthesis
Repriming
Fork reversal
DNA replication
Replication stress
S-phase checkpoint
Genomic instability
Ciencias de la vida
Acceso en línea:http://repositoriouba.sisbi.uba.ar/gsdl/cgi-bin/library.cgi?a=d&c=posgraafa&cl=CL1&d=HWA_7897
https://repositoriouba.sisbi.uba.ar/gsdl/collect/posgraafa/index/assoc/HWA_7897.dir/7897.PDF
Aporte de:
Repositorio Digital de la Universidad de Buenos Aires (UBA) de Universidad de Buenos Aires
Descripción
Sumario:DNA replication is a key event for life as well as the trigger for diseases such as cancer. Failed or incomplete replication can generate genomic instability, an event that precedes genomic rearrangements that promote carcinogenesis. The success of the replication process depends on the correct execution of replicative elongation and origin firing events. During my PhD I found that a DNA polymerase, Pol iota (?), constrains these parameters to, counterintuitively, achieve greater success in the completion of the replicative program. Mechanistically, Pol ? expression deficiency triggers an excessive involvement of the DNA polymerase PrimPol in replication, leading to a reduction in signals that prevent the passage to M phase with under-replicated DNA content, triggering genomic instability. This function of Pol ?, requires its interaction with the replisome recruitment platform, PCNA, and is independent of its polymerase activity, suggesting an effect associated with the modulation of replisome composition. Our findings unveil an unforeseen role of Pol ? in protecting genomic stability from deleterious effects caused by PrimPol overutilization.

Ejemplares similares