Leishmania major chromosomes are replicated from a single high-efficiency locus supplemented by thousands of lower efficiency initiation events.

Jeziel D Damasceno, Gabriel L A Silva, Catarina A Marques, Marija Krasilnikova, Craig Lapsley, Dario Beraldi, Richard McCulloch

Abstract read

PubMed Full text at PMC Publisher

In one paragraph

Article in Cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it

0cells of the map it votes in

3citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

Genome-wide mapping of replication stress response factors reveals the management of polycistronic transcription, replication initiation, and responses to replication stress in Leishmania.Nucleic acids research · 2026
Article
Kinetoplast-Directed Therapies: A Selective Mitochondrial Approach to Combat Leishmaniasis.Pharmaceuticals (Basel, Switzerland) · 2026
Review
Automated mapping of DNA replication fork progression in human cells with ForkML.Nature communications · 2026
Article

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Jeziel D DamascenoThe University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place, G12 8TA Glasgow, UK. Electronic address: jeziel.damasceno@glasgow.ac.uk.

Gabriel L A SilvaThe University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place, G12 8TA Glasgow, UK.

Catarina A MarquesThe University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place, G12 8TA Glasgow, UK.

Marija KrasilnikovaThe University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place, G12 8TA Glasgow, UK.

Craig LapsleyThe University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place, G12 8TA Glasgow, UK.

Dario BeraldiThe University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place, G12 8TA Glasgow, UK.

Richard McCullochThe University of Glasgow Centre for Parasitology, The Wellcome Centre for Integrative Parasitology, University of Glasgow, School of Infection and Immunity, Sir Graeme Davies Building, 120 University Place, G12 8TA Glasgow, UK. Electronic address: richard.mcculloch@glasgow.ac.uk.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

DNA replication initiates at genome sites termed origins. Previous origin mapping approaches in the populations of the protozoan parasite Leishmania major were discordant, suggesting either a single origin per chromosome or 200-fold more origins. To reconcile these data and fully understand DNA replication dynamics, we have applied DNAscent, an assay that detects patterns of 5-bromodeoxyuridine (BrdU) incorporation in individual long-read DNA molecules. We confirm the pre-eminence of a single locus of DNA replication initiation in each chromosome and reveal a much larger number of lower-efficiency DNA replication initiation events whose abundance is greater as chromosome size increases. Each initiation site is a region of high AT content, increased G-quadruplex levels, lowered chromatin occupancy, and reduced levels of nascent RNA. Finally, we show that all DNA replication initiation results in mutagenesis. This work reveals a bimodal strategy for DNA replication programming in Leishmania that drives replication timing and sequence variation.

Indexed as

ChromosomesDNA ReplicationGenetic LociLeishmania majorChromatinG-QuadruplexesReplication OriginChromatinaneuploidyCP: Molecular biologyDNA replicationDNAscentgenome plasticitygenome stabilityLeishmanialong-read sequencingOringinsreplication timing

Identifiers

PMID40768333

DOI10.1016/j.celrep.2025.116094

PMCPMC12890776

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.