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

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...

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Autores principales: Totañes, Francis Isidore Garcia, Gockel, Jonas, Chapman, Sarah E, Bártfai, Richárd, Boemo, Michael A, Merrick, Catherine J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10085703/
https://www.ncbi.nlm.nih.gov/pubmed/36808528
http://dx.doi.org/10.1093/nar/gkad093
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author Totañes, Francis Isidore Garcia
Gockel, Jonas
Chapman, Sarah E
Bártfai, Richárd
Boemo, Michael A
Merrick, Catherine J
author_facet Totañes, Francis Isidore Garcia
Gockel, Jonas
Chapman, Sarah E
Bártfai, Richárd
Boemo, Michael A
Merrick, Catherine J
author_sort Totañes, Francis Isidore Garcia
collection PubMed
description 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.
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spelling pubmed-100857032023-04-11 A genome-wide map of DNA replication at single-molecule resolution in the malaria parasite Plasmodium falciparum Totañes, Francis Isidore Garcia Gockel, Jonas Chapman, Sarah E Bártfai, Richárd Boemo, Michael A Merrick, Catherine J Nucleic Acids Res Genome Integrity, Repair and Replication 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. Oxford University Press 2023-02-20 /pmc/articles/PMC10085703/ /pubmed/36808528 http://dx.doi.org/10.1093/nar/gkad093 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Genome Integrity, Repair and Replication
Totañes, Francis Isidore Garcia
Gockel, Jonas
Chapman, Sarah E
Bártfai, Richárd
Boemo, Michael A
Merrick, Catherine J
A genome-wide map of DNA replication at single-molecule resolution in the malaria parasite Plasmodium falciparum
title A genome-wide map of DNA replication at single-molecule resolution in the malaria parasite Plasmodium falciparum
title_full A genome-wide map of DNA replication at single-molecule resolution in the malaria parasite Plasmodium falciparum
title_fullStr A genome-wide map of DNA replication at single-molecule resolution in the malaria parasite Plasmodium falciparum
title_full_unstemmed A genome-wide map of DNA replication at single-molecule resolution in the malaria parasite Plasmodium falciparum
title_short A genome-wide map of DNA replication at single-molecule resolution in the malaria parasite Plasmodium falciparum
title_sort genome-wide map of dna replication at single-molecule resolution in the malaria parasite plasmodium falciparum
topic Genome Integrity, Repair and Replication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10085703/
https://www.ncbi.nlm.nih.gov/pubmed/36808528
http://dx.doi.org/10.1093/nar/gkad093
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