Genome duplication in Leishmania major relies on persistent subtelomeric DNA replication

Author(s)

Damasceno, Jeziel Dener ^[1] ; Marques, Catarina A. ^[1] ; Beraldi, Dario ^[1] ; Crouch, Kathryn ^[1] ; Lapsley, Craig ^[1] ; Obonaga, Ricardo ^[2] ; Tosi, Luiz R. O. ^[2] ; McCulloch, Richard ^[1]

Affiliation

^[1] Univ Glasgow, Wellcome Ctr Integrat Parasitol, Inst Infect Immun & Inflammat, Glasgow, Lanark - Scotland

^[2] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Cell & Mol Biol, Ribeirao Preto - Brazil

• Document type: Journal article
• Source: eLIFE; v. 9, SEP 8 2020.
• Web of Science Citations: 2

Abstract

DNA replication is needed to duplicate a cell's genome in S phase and segregate it during cell division. Previous work in Leishmania 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 Leishmania'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. (AU)

• FAPESP's process: 17/07092-9 - How do checkpoint proteins Rad9 and Hus1 act to maintain genome stability in the protozoan Leishmania major?
• Grantee: Luiz Ricardo Orsini Tosi
• Support Opportunities: Regular Research Grants