Nuclear DNA replication in trypanosomatids: there are no easy methods for solving difficult problems

da Silva, M. S., Pavani, R. S., Damasceno, J. D. , Marques, C. A. , McCulloch, R. , Tosi, L. R. O. and Elias, M. C. (2017) Nuclear DNA replication in trypanosomatids: there are no easy methods for solving difficult problems. Trends in Parasitology, 33(11), pp. 858-874. (doi: 10.1016/j.pt.2017.08.002) (PMID:28844718) (PMCID:PMC5662062)

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Abstract

In trypanosomatids, etiological agents of devastating diseases, replication is robust and finely controlled to maintain genome stability and function in stressful environments. However, these parasites encode several replication protein components and complexes that show potentially variant composition compared with model eukaryotes. This review focuses on the advances made in recent years regarding the differences and peculiarities of the replication machinery in trypanosomatids, including how such divergence might affect DNA replication dynamics and the replication stress response. Comparing the DNA replication machinery and processes of parasites and their hosts may provide a foundation for the identification of targets that can be used in the development of chemotherapies to assist in the eradication of diseases caused by these pathogens.

Item Type:Articles
Keywords:DNA replication, origin recognition complex, replication fork, replication origins, replication stress, trypanosomatid emergence.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Damasceno, Dr Jeziel and McCulloch, Professor Richard and De Almeida Marques, Dr Catarina
Authors: da Silva, M. S., Pavani, R. S., Damasceno, J. D., Marques, C. A., McCulloch, R., Tosi, L. R. O., and Elias, M. C.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Trends in Parasitology
Publisher:Elsevier (Cell Press)
ISSN:1471-4922
ISSN (Online):1471-5007
Published Online:24 August 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Trends in Parasitology 33(11): 858-874
Publisher Policy:Reproduced under a Creative Commons License

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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
463981Characterisation of Orc1/Cdc6 and DNA replication initiation in Trypanosoma brucei.Richard McCullochWellcome Trust (WELLCOTR)083485/Z/07/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
716221How 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
68706114CONFAP Understanding diverged genome repair and replication functions in trypanosomatid parasitesRichard McCullochBiotechnology and Biological Sciences Research Council (BBSRC)BB/M028909/1III - PARASITOLOGY
371799The Wellcome Centre for Molecular Parasitology ( Core Support )Andrew WatersWellcome Trust (WELLCOTR)104111/Z/14/Z & AIII - PARASITOLOGY
623593Institutional Strategic Support Fund (ISSF)Anna DominiczakWellcome Trust (WELLCOTR)105614/Z/14/ZRI CARDIOVASCULAR & MEDICAL SCIENCES