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A genome-wide map of DNA replication at single-molecule resolution in the malaria parasite Plasmodium falciparum.

Published version
Peer-reviewed

Repository DOI


Type

Article

Change log

Authors

Totañes, Francis Isidore Garcia 
Gockel, Jonas 
Chapman, Sarah E 
Boemo, Michael A 

Abstract

The malaria parasite Plasmodium falciparum replicates via schizogony: an unusual type of cell cycle involving asynchronous replication of multiple nuclei within the same cytoplasm. Here, we present the first comprehensive study of DNA replication origin specification and activation during Plasmodium schizogony. Potential replication origins were abundant, with ORC1-binding sites detected every ∼800 bp. In this extremely A/T-biased genome, the sites were biased towards areas of higher G/C content, and contained no specific sequence motif. Origin activation was then measured at single-molecule resolution using newly developed DNAscent technology: a powerful method of detecting replication fork movement via base analogues in DNA sequenced on the Oxford Nanopore platform. Unusually, origins were preferentially activated in areas of low transcriptional activity, and replication forks also moved fastest through lowly transcribed genes. This contrasts with the way that origin activation is organised in other systems, such as human cells, and suggests that P. falciparum has evolved its S-phase specifically to minimise conflicts between transcription and origin firing. This may be particularly important to maximise the efficiency and accuracy of schizogony, with its multiple rounds of DNA replication and its absence of canonical cell-cycle checkpoints.

Description

Keywords

Animals, Humans, Plasmodium falciparum, Parasites, Malaria, Falciparum, DNA Replication, Cell Cycle, Replication Origin

Journal Title

Nucleic Acids Res

Conference Name

Journal ISSN

0305-1048
1362-4962

Volume Title

51

Publisher

Oxford University Press (OUP)
Sponsorship
EPSRC (EP/T022159/1)
European Research Council (725126)