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Título

Histone depletion prevents telomere-telomere fusions in pre-senescent cells

AutorBarrientos-Moreno, Marta; Murillo-Pineda, Marina ; Muñoz-Cabello, Ana M. ; Prado, Félix
Fecha de publicación2016
EditorSociedad Española de Bioquímica y Biología Molecular
CitaciónXXXIX Congreso SEBBM (2016)
ResumenNucleosome assembly during DNA replication establishes the primary chromatin structure, which is essential for genome organization and stability. Defective chromatin assembly causes replication fork instability and hyper-recombination, and impairs sister-chromatid decatenation and chromosome bi-orientation during mitosis. The importance of nucleosome assembly in genome integrity is also highlighted by the fact that replicative aging in yeast and replicative senescence in yeast and humans are associated with a severe reduction in the amount of histones. Telomere shortening can prevent tumour development by inducing senescence of transformed cells; however, it can also lead to cancer initiation by inducing chromosomal instability because cells divide during pre-senescence with critically short telomeres that can be recognize as unrepaired breaks and be fused to other telomeres (telomere-telomere fusions; T-TFs) or DSBs, thus causing gross chromosomal rearrangements. Here we show that histone depletion prevents T-TFs in mecl∆ tell∆ cells defective in telomere maintenance. Since pre-senescence in cells lacking the telomerase has been shown to be associated with a reduction in the pool of available histones through a Mecl-dependent mechanism, we hypothesize that histone depletion is an active mechanism to protect telomeres that is lost in mecl∆ tell∆ cells. This mechanism is independent of the telomerase but strictly dependent on homologous recombination. We propose that the increase in recombination by replication fork collapse as a consequence of the deficit of histones protects short telomeres during pre-senescence.
DescripciónResumen del póster presentado al XXXIX Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Salamanca del 5 al 8 de septiembre de 2016.
URIhttp://hdl.handle.net/10261/165843
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