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Tissue-Specific Requirement for the GINS Complex During Zebrafish Development

Varga, M; Csályi, K; Bertyák, I; Menyhárd, DK; Poole, RJ; Cerveny, KL; Kövesdi, D; ... Wilson, SW; + view all (2020) Tissue-Specific Requirement for the GINS Complex During Zebrafish Development. Frontiers in Cell and Developmental Biology , 8 , Article 373. 10.3389/fcell.2020.00373. Green open access

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Abstract

Efficient and accurate DNA replication is particularly critical in stem and progenitor cells for successful proliferation and survival. The replisome, an amalgam of protein complexes, is responsible for binding potential origins of replication, unwinding the double helix, and then synthesizing complimentary strands of DNA. According to current models, the initial steps of DNA unwinding and opening are facilitated by the CMG complex, which is composed of a GINS heterotetramer that connects Cdc45 with the mini-chromosome maintenance (Mcm) helicase. In this work, we provide evidence that in the absence of GINS function DNA replication is cell autonomously impaired, and we also show that gins1 and gins2 mutants exhibit elevated levels of apoptosis restricted to actively proliferating regions of the central nervous system (CNS). Intriguingly, our results also suggest that the rapid cell cycles during early embryonic development in zebrafish may not require the function of the canonical GINS complex as neither zygotic Gins1 nor Gins2 isoforms seem to be present during these stages.

Type: Article
Title: Tissue-Specific Requirement for the GINS Complex During Zebrafish Development
Location: Switzerland
Open access status: An open access version is available from UCL Discovery
DOI: 10.3389/fcell.2020.00373
Publisher version: http://dx.doi.org/10.3389/fcell.2020.00373
Language: English
Additional information: © 2020 Varga, Csályi, Bertyák, Menyhárd, Poole, Cerveny, Kövesdi, Barátki, Rouse, Vad, Hawkins, Stickney, Cavodeassi, Schwarz, Young and Wilson. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Keywords: CMG complex, GINS complex, GINS2, proliferation, replication, zebrafish
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Cell and Developmental Biology
URI: https://discovery.ucl.ac.uk/id/eprint/10102191
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