Conservation and Variation in Strategies for DNA Replication of Kinetoplastid Nuclear Genomes

Current Genomics
Catarina A Marques, Richard McCulloch

Abstract

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...Continue Reading

Citations

Sep 13, 2019·PLoS Genetics·Babatunde Ekundayo, Franziska Bleichert
Jun 24, 2020·BMC Genomics·Christiane Bezerra de AraujoMaria Carolina Elias
Sep 11, 2019·Annual Review of Microbiology·Richard J WheelerJack D Sunter

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Methods Mentioned

BETA
gel filtration
fluorescence activated cell sorting
MFA-seq
immunoprecipitation
ChIP-seq

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