Conservation and variation in strategies for DNA replication of kinetoplastid nuclear genomes

Marques, C. A. and McCulloch, R. (2018) Conservation and variation in strategies for DNA replication of kinetoplastid nuclear genomes. Current Genomics, 19(2), pp. 98-109. (doi:10.2174/1389202918666170815144627) (PMID:29491738) (PMCID:PMC5814967)

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Introduction: Understanding how the nuclear genome of kinetoplastid parasites is replicated received experimental stimulus from sequencing of the Leishmania major, Trypanosoma brucei and Trypanosoma cruzi genomes around 10 years ago. Gene annotations suggested key players in DNA replication initiation could not be found in these organisms, despite considerable conservation amongst characterised eukaryotes. Initial studies that indicated trypanosomatids might possess an archaeal- like origin recognition complex (ORC), composed of only a single factor termed ORC1/CDC6, have been supplanted by the more recent identification of an ORC in T. brucei. However, the constituent subunits of T. brucei ORC are highly diverged relative to other eukaryotic ORCs and the activity of the complex appears subject to novel, positive regulation. The availability of whole genome sequences has also allowed the deployment of genome-wide strategies to map DNA replication dynamics, to date in T. brucei and Leishmania. ORC1/CDC6 binding and function in T. brucei displays pronounced overlap with the unconventional organisation of gene expression in the genome. Moreover, mapping of sites of replication initiation suggests pronounced differences in replication dynamics in Leishmania relative to T. brucei. Conclusion: Here we discuss what implications these emerging data may have for parasite and eukaryotic biology of DNA replication.

Item Type:Articles
Glasgow Author(s) Enlighten ID:McCulloch, Professor Richard and De Almeida Marques, Dr Catarina
Authors: Marques, C. A., and McCulloch, R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Current Genomics
Publisher:Bentham Science Publishers Ltd.
ISSN (Online):1875-5488
Published Online:15 August 2017
Copyright Holders:Copyright © 2017 Bentham Science Publishers Ltd.
First Published:First published in Current Genomics 19(2): 98-109
Publisher Policy:Reproduced in accordance with the publisher copyright policy

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
515891Chromosomal recombination and repair in African trypanosomesRichard McCullochWellcome Trust (WELLCOTR)089172/Z/09/ZIII - PARASITOLOGY
558541Do DNA double strand breaks initiate antigenic variation by homologous recombination in Trypanossoma brucei?Richard McCullochWellcome Trust (WELLCOTR)093589/Z/10/ZIII - PARASITOLOGY
606431Kinase dependent control of DNA replication and repair as a drug target in Trypanosoma brucei.Richard McCullochBiotechnology and Biological Sciences Research Council (BBSRC)BB/K006495/1III - PARASITOLOGY
371799The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/Z & AIII - PARASITOLOGY