Genome duplication in Leishmania major relies on persistent subtelomeric DNA replication.
Genome duplication in Leishmania major relies on persistent subtelomeric DNA replication.
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DOI：
10.7554/elife.58030
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发表时间：
2020-09-08
期刊：
影响因子：
7.7
通讯作者：
McCulloch R
中科院分区：
文献类型：
--
作者：
Damasceno JD;Marques CA;Beraldi D;Crouch K;Lapsley C;Obonaga R;Tosi LR;McCulloch R
DNA复制需要在S期复制细胞的基因组并在细胞分裂期间分离它。先前在利什曼原虫中的工作仅在每条染色体中的单个区域检测到DNA复制起始，预测该组织不足以在S期内进行完整的基因组复制。在这里，我们表明，乙酰化组蛋白H3（AcH 3），基地J和动粒因子共定位在每个染色体中只有一个单一的基因座，这对应于以前映射的DNA复制起始区域，并划定本地化的G/T偏斜和G4模式。此外，我们描述了G2/M和G1期富集细胞中以前未检测到的亚端粒DNA复制。最后，我们表明，亚端粒DNA复制，不像染色体内部的DNA复制，是敏感的羟基脲和依赖于9-1-1活动。这些研究结果表明，利什曼原虫的基因组复制程序采用亚端粒DNA复制启动，可能延伸到S期以外，以支持主要是染色体内部的DNA复制启动S期内。
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.