Genome duplication in Leishmania major relies on persistent subtelomeric DNA replication

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
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Crouch, Dr Kathryn and Beraldi, Dr Dario and Damasceno, Dr Jeziel and Lapsley, Mr Craig and McCulloch, Professor Richard
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
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 > Institute of Infection Immunity and Inflammation
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
173173How do common and diverged features of the replicative stress response shape the biology of TriTrypRichard McCullochBiotechnology and Biological Sciences Research Council (BBSRC)BB/N016165/1III - Parasitology
301963Does genome replication in the protozoan parasite Leishmania rely on origin-indepenent initiation?Richard McCullochBiotechnology and Biological Sciences Research Council (BBSRC)BB/R017166/1III - Parasitology
173959RECREPEMLERichard McCullochEuropean Commission (EC)750259III - Parasitology
170547The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/ZRIII - Parasitology