The EMBO journal, 2017-11, Vol.36 (21), p.3212-3231
2017
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Details
- Autor(en) / Beteiligte
- Titel
- Initiation of DNA replication requires actin dynamics and formin activity
- Ist Teil von
- The EMBO journal, 2017-11, Vol.36 (21), p.3212-3231
- Ort / Verlag
- England: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2017
- Quelle
- Wiley Online Library - AutoHoldings Journals
- Beschreibungen/Notizen
- 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. Synopsis Regulation of actin dynamics affects both the initiation and elongation steps of DNA replication in human cells and Xenopus egg extracts, through various mechanisms including nuclear transport and chromatin loading of replication factors. Nuclear actin dynamics are required for DNA replication in embryonic and somatic cell systems. Disrupting actin dynamics or inhibiting formin proteins blocks nuclear transport. Nuclear actin interactions with RanGTP–importin complexes control cargo release. Nuclear formin activity promotes chromatin localisation of replication factors. Regulation of actin dynamics affects DNA synthesis in human cells and Xenopus egg extracts through multiple mechanisms, including nuclear transport and chromatin loading of replication factors.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0261-4189eISSN: 1460-2075DOI: 10.15252/embj.201796585Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5666611
- Format
- –
- Schlagworte
- Actin, Actins - genetics, Actins - metabolism, Active Transport, Cell Nucleus - genetics, Animals, Cell Line, Tumor, Cell Nucleus - metabolism, Cellular Biology, Chromatin, Chromatin - chemistry, Chromatin - metabolism, Complex Mixtures - chemistry, Cyclin-dependent kinase, Cytoplasm - metabolism, Deoxyribonucleic acid, DNA, DNA biosynthesis, DNA damage, DNA Replication, Dynamics, Elongation, Embryos, Epithelial Cells - cytology, Epithelial Cells - metabolism, Fetal Proteins - genetics, Fetal Proteins - metabolism, formin, Formins, Gene Expression Regulation, HeLa Cells, Humans, Karyopherins - genetics, Karyopherins - metabolism, Life Sciences, Loads (forces), Localization, Microfilament Proteins - genetics, Microfilament Proteins - metabolism, Nuclear Localization Signals, Nuclear Proteins - genetics, Nuclear Proteins - metabolism, Nuclear transport, Polymerization, Proliferating cell nuclear antigen, Proliferating Cell Nuclear Antigen - genetics, Proliferating Cell Nuclear Antigen - metabolism, Proteins, ran GTP-Binding Protein - genetics, ran GTP-Binding Protein - metabolism, Regulators, Replication, Replication initiation, Signal Transduction, Somatic cells, Transcription, Transcription, Genetic, Transport, Xenopus, Xenopus laevis, Zygote - chemistry