Initiation of DNA Replication Requires Actin Dynamics and Formin Activity

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2017 Oct 7

PMID 28982779

Citations 50

Authors

Nikolaos Parisis

Liliana Krasinska

Bethany Harker

Serge Urbach

Michel Rossignol

Alain Camasses

James Dewar

Nathalie Morin

Daniel Fisher

Affiliations

Soon will be listed here.

Abstract

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 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 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.

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