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EMBO J 2017 Nov 02;3621:3212-3231. doi: 10.15252/embj.201796585.
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Initiation of DNA replication requires actin dynamics and formin activity.

Parisis N , Krasinska L , Harker B , Urbach S , Rossignol M , Camasses A , Dewar J , Morin N , Fisher D .

Nuclear actin regulates transcriptional programmes in a manner dependent on its levels and polymerisation state. This dynamics is determined by the balance of nucleocytoplasmic shuttling, formin- and redox-dependent filament polymerisation. Here, using Xenopus egg extracts and human somatic cells, we show that actin dynamics and formins are essential for DNA replication. In proliferating cells, formin inhibition abolishes nuclear transport and initiation of DNA replication, as well as general transcription. In replicating nuclei from transcriptionally silent Xenopus egg extracts, we identified numerous actin regulators, and disruption of actin dynamics abrogates nuclear transport, preventing NLS (nuclear localisation signal)-cargo release from RanGTP-importin complexes. Nuclear formin activity is further required to promote loading of cyclin-dependent kinase (CDK) and proliferating cell nuclear antigen (PCNA) onto chromatin, as well as initiation and elongation of DNA replication. Therefore, actin dynamics and formins control DNA replication by multiple direct and indirect mechanisms.

PubMed ID: 28982779
PMC ID: PMC5666611
Article link: EMBO J

Species referenced: Xenopus laevis
Genes referenced: fmn1

References [+] :
Allen, Visualization of the nucleus and nuclear envelope in situ by SEM in tissue culture cells. 2007, Pubmed, Xenbase