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RECREPEMLE

Recombination-derived replication in the eukaryotic microbe Leishmania: a genome-wide process?

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EC-Contrib. €

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Project "RECREPEMLE" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY OF GLASGOW 

Organization address
address: UNIVERSITY AVENUE
city: GLASGOW
postcode: G12 8QQ
website: www.gla.ac.uk

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country United Kingdom [UK]
 Project website https://www.gla.ac.uk/researchinstitutes/iii/staff/richardmcculloch/
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-10-01   to  2019-09-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF GLASGOW UK (GLASGOW) coordinator 183˙454.00

Map

 Project objective

In any organism, the need to reproduce is paramount, with genome replication being the earliest step in the process. The machinery and mechanisms of DNA replication are widely conserved, with initiation occurring at defined bi-directional DNA synthesis sites termed origins. Though origins may not be conserved DNA sequences, they are defined through binding conserved replication initiator factors. In some circumstances, such as after DNA damage or origin deletion, origin-independent replication can be observed in cellular organisms and can be driven by recombination. However, origin-independent replication is not normally considered to be a genome-wide, central reaction of genome replication. Very recently, genome-wide mapping of DNA replication initiation in two species of the kinetoplastid parasite Leishmania revealed only a single locus-specific origin per chromosome. Analyses of Leishmania S phase length and DNA synthesis speed suggest that a single origin-based strategy is insufficient for complete genome duplication, indicating replication in these eukaryotic microbes relies on origin-independent initiation to support origin-directed initiation. In this proposal, I will test the hypothesis that stochastic origin-independent DNA synthesis initiation events occur throughout the Leishmania genome due to homologous recombination acting on DNA lesions. If correct, this work will reveal the first example of a cellular organism that uses origin-independent replication as a core feature of genome duplication. The genome-wide use of recombination-driven replication would alter our view of DNA replication evolution and would explain the remarkable genome plasticity of Leishmania, with implications for how the parasite adapts genome structure and gene expression in the face of changing environments. Such adaptive change is seen during acquisition of resistance to anti-leishmanial drugs, and so this work will provide insight into the use and development of therapies.

 Publications

year authors and title journal last update
List of publications.
2019 Jeziel D. Damasceno, João Reis-Cunha, Kathryn Crouch, Craig Lapsley, Luiz R. O. Tosi, Daniella Bartholomeu, Richard McCulloch
Conditional knockout of RAD51-related genes in Leishmania major reveals a critical role for homologous recombination during genome replication
published pages: , ISSN: , DOI: 10.1101/800573
2020-03-11
2019 Jeziel D. Damasceno, Catarina A. Marques, Dario Beraldi, Kathryn Crouch, Craig Lapsley, Ricardo Obonaga, Luiz R. O. Tosi, Richard McCulloch
Genome duplication in Leishmania major relies on DNA replication outside S phase
published pages: , ISSN: , DOI: 10.1101/799429
2020-03-11

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