Title:Conservation and Variation in Strategies for DNA Replication of Kinetoplastid Nuclear Genomes
VOLUME: 19 ISSUE: 2
Author(s):Catarina A. Marques* and Richard McCulloch*
Affiliation:Division of Biological Chemistry and Drug Discovery, School of Life Sciences, Dow Street, University of Dundee, Dundee, DD1 5EH, The Wellcome Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, Sir Graeme Davis Building, 120 University Place, University of Glasgow, Glasgow, G12 8TA
Keywords:DNA replication, Origin recognition complex (ORC), Origins of replication, Trypanosoma brucei, Leishmania,
Kinetoplastid parasites.
Abstract: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.
