Damasceno, J. D. , Marques, C. A. , Beraldi, D., Crouch, K. , Lapsley, C., Obonaga, R., Tosi, L. R.O. and McCulloch, R. (2020) Genome duplication in Leishmania major relies on persistent subtelomeric DNA replication. eLife, 9, e58030. (doi: 10.7554/eLife.58030) (PMID:32897188) (PMCID:PMC7511235)
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Abstract
DNA replication is needed to duplicate a cell’s genome in S phase and segregate it during cell division. Previous work in Leishmania detected DNA replication initiation at just a single region in each chromosome, an organisation predicted to be insufficient for complete genome duplication within S phase. Here, we show that acetylated histone H3 (AcH3), base J and a kinetochore factor co-localise in each chromosome at only a single locus, which corresponds with previously mapped DNA replication initiation regions and is demarcated by localised G/T skew and G4 patterns. In addition, we describe previously undetected subtelomeric DNA replication in G2/M and G1-phase-enriched cells. Finally, we show that subtelomeric DNA replication, unlike chromosome-internal DNA replication, is sensitive to hydroxyurea and dependent on 9-1-1 activity. These findings indicate that Leishmania’s genome duplication programme employs subtelomeric DNA replication initiation, possibly extending beyond S phase, to support predominantly chromosome-internal DNA replication initiation within S phase.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Damasceno, Dr Jeziel and Lapsley, Mr Craig and McCulloch, Professor Richard and Crouch, Dr Kathryn and Beraldi, Dr Dario and De Almeida Marques, Dr Catarina |
Creator Roles: | Damasceno, J.Conceptualization, Resources, Data curation, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing – original draft, Writing – review and editing Beraldi, D.Data curation, Software, Formal analysis, Validation, Investigation, Methodology, Writing – review and editing Crouch, K.Resources, Data curation, Software, Formal analysis, Supervision, Methodology, Investigation, Writing – review and editing Lapsley, C.Formal analysis, Validation, Investigation, Writing – review and editing McCulloch, R.Conceptualization, Formal analysis, Supervision, Funding acquisition, Investigation, Methodology, Writing – original draft, Project administration, Writing – review and editing Marques, C. A.Conceptualization, Resources, Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review and editing |
Authors: | Damasceno, J. D., Marques, C. A., Beraldi, D., Crouch, K., Lapsley, C., Obonaga, R., Tosi, L. R.O., and McCulloch, R. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
Journal Name: | eLife |
Publisher: | eLife Sciences Publications |
ISSN: | 2050-084X |
ISSN (Online): | 2050-084X |
Copyright Holders: | Copyright © 2020 The Authors |
First Published: | First published in eLife 9:e58030 |
Publisher Policy: | Reproduced under a Creative Commons License |
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