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RECREPEMLE

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

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
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RECREPEMLE project word cloud

Explore the words cloud of the RECREPEMLE project. It provides you a very rough idea of what is the project "RECREPEMLE" about.

environments view homologous deletion species correct changing locus organism though length recombination duplication genome earliest chromosome stochastic revealed binding hypothesis adapts insufficient initiator suggest bi occurring first paramount microbes relies origin complete initiation parasite sites normally acting strategy lesions acquisition dna independent sequences implications gene kinetoplastid expression core cellular directed indicating therapies termed events resistance structure leishmanial central synthesis reproduce organisms evolution mapping plasticity replication alter eukaryotic directional origins leishmania circumstances uses conserved machinery damage mechanisms remarkable reveal anti reaction speed single adaptive drugs

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 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.	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

List of publications.
year	authors and title	journal	last update
2019	Jeziel D. Damasceno, JoÃ£o 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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