Data di Pubblicazione:
2018
Citazione:
Epigenetic regulation of eukaryotic DNA replication origins / L. Falbo, E. Raspelli, F. Romeo, V. Costanzo. ((Intervento presentato al 14. convegno SIBBM : Frontiers in Molecular Biology – When and where : temporal and spatial regulation of biological processes tenutosi a Roma nel 2018.
Abstract:
In higher eukaryotes, DNA replication initiates at multiple sites distributed along the
chromosome, called replication origins. The location and timing of these initiation events are
developmentally and epigenetically regulated. In the early Xenopus embryos replication
origins are more abundant than in somatic cells, or at later stages of development. This
particular organization of the replicon ensures rapid and accurate genome duplication during
early embryonic cell divisions. Close to the mid-blastula transition (MBT), the density of
replication origins declines, initiation of DNA replication becomes restricted to specific sites
and correlates with cell cycle lengthening. Intriguingly, in nuclear transfer
experiments exposure of somatic nuclei to egg cytoplasm is sufficient to convert the somatic
origin density to the embryonic one, suggesting that the replication origin assembly in somatic
cells is restrained by epigenetic factors modifiable by the egg cytoplasm. We performed
extensive biochemical fraction of egg cytoplasm to identify factors that regulate replication
origin density in embryonic and somatic nuclei. This effort led to the isolation of SSRP1 as
major factor that stimulates somatic nuclei replication in egg extract. We showed that
exposure of somatic nuclei to SSRP1 removes epigenetic determinants that restrain
replication origin assembly and restores replication origin density typical of embryonic nuclei
on somatic chromatin. Strikingly, SSRP1-mediated regulation of replication origin assembly
has a dramatic impact on cell cycle progression and early embryonic development. These
results and their implications will be described in details in the context of more general
regulation of DNA replication in vertebrate organisms.
Tipologia IRIS:
14 - Intervento a convegno non pubblicato
Keywords:
Replication origins; Xenopus; epigenetic
Elenco autori:
L. Falbo, E. Raspelli, F. Romeo, V. Costanzo
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