Genome duplication in Leishmania major relies on persistent subtelomeric DNA replication

DNA replication is needed to duplicate a cell's genome in S phase and segregate it during cell division. Previous work in detected DNA replication initiation at just a single region in each chromosome, an organisation predicted to be insufficient for complete genome duplication within S phase....

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Bibliographic Details
Published in:eLife 2020-09, Vol.9
Main Authors: Damasceno, Jeziel Dener, Marques, Catarina A, Beraldi, Dario, Crouch, Kathryn, Lapsley, Craig, Obonaga, Ricardo, Tosi, Luiz Ro, McCulloch, Richard
Format: Article
Language:English
Subjects:
Chromosome Structures - chemistry
Chromosome Structures - genetics
Chromosome Structures - metabolism
Chromosomes - chemistry
Chromosomes - genetics
DNA replication
DNA Replication - genetics
Gene Duplication - genetics
Genetics and Genomics
Genome, Protozoan - genetics
Histones - genetics
Histones - metabolism
Leishmania
Leishmania major - genetics
Microbiology and Infectious Disease
origin
S Phase - genetics
subtelomere
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Summary:DNA replication is needed to duplicate a cell's genome in S phase and segregate it during cell division. Previous work in detected DNA replication initiation at just a single region in each chromosome, an organisation predicted to be insufficient for complete genome duplication within S phase. Here, we show that acetylated histone H3 (AcH3), base J and a kinetochore factor co-localise in each chromosome at only a single locus, which corresponds with previously mapped DNA replication initiation regions and is demarcated by localised G/T skew and G4 patterns. In addition, we describe previously undetected subtelomeric DNA replication in G2/M and G1-phase-enriched cells. Finally, we show that subtelomeric DNA replication, unlike chromosome-internal DNA replication, is sensitive to hydroxyurea and dependent on 9-1-1 activity. These findings indicate that 's genome duplication programme employs subtelomeric DNA replication initiation, possibly extending beyond S phase, to support predominantly chromosome-internal DNA replication initiation within S phase.
ISSN:2050-084X
2050-084X
DOI:10.7554/ELIFE.58030