Replication timing analysis in polyploid cells reveals Rif1 uses multiple mechanisms to promote underreplication in Drosophila.
Replication timing analysis in polyploid cells reveals Rif1 uses multiple mechanisms to promote underreplication in Drosophila.
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DOI：
10.1093/genetics/iyab147
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发表时间：
2021-11-05
期刊：
影响因子：
3.3
通讯作者：
Nordman J
中科院分区：
文献类型：
--
作者：
Das S;Caballero M;Kolesnikova T;Zhimulev I;Koren A;Nordman J
DNA复制和拷贝数的调节是促进基因组稳定性和维持细胞和组织功能所必需的。DNA复制在一个称为复制定时（RT）的过程中受到时间上的调节。Rap1相互作用因子1（Rif1）是RT的关键调节因子，在多倍体细胞中的拷贝数控制中具有关键功能。以前，我们证明了Rif1与SUUR一起发挥作用，以抑制复制叉进展并促进特定基因组区域的复制不足（UR）。Rif1依赖的RT控制因素如何影响其促进UR的能力尚不清楚。通过应用计算方法来测量果蝇多倍体细胞中的RT，我们表明，SUUR和Rif1在控制UR和RT中具有不同的作用。我们的研究结果表明，Rif1的行为，以促进后期复制，这是必要的SUUR依赖的复制不足。我们的工作提供了新的洞察过程中的UR和它的联系RT。在多倍体细胞中，拷贝数是不均匀的整个基因组。复制不足导致臂间异染色质和常染色质的限定区域相对于总体倍性具有减少的拷贝数。SUUR和Rif1是复制不足的关键调节因子，Rif1是已知的复制定时（RT）调节因子。Das等人采用计算方法来测量多倍体细胞中的复制时间。他们的结果表明，虽然Rif1和SUUR都促进了复制不足，但它们对RT的影响不同。
Regulation of DNA replication and copy number is necessary to promote genome stability and maintain cell and tissue function. DNA replication is regulated temporally in a process known as replication timing (RT). Rap1-interacting factor 1 (Rif1) is a key regulator of RT and has a critical function in copy number control in polyploid cells. Previously, we demonstrated that Rif1 functions with SUUR to inhibit replication fork progression and promote underreplication (UR) of specific genomic regions. How Rif1-dependent control of RT factors into its ability to promote UR is unknown. By applying a computational approach to measure RT in Drosophila polyploid cells, we show that SUUR and Rif1 have differential roles in controlling UR and RT. Our findings reveal that Rif1 acts to promote late replication, which is necessary for SUUR-dependent underreplication. Our work provides new insight into the process of UR and its links to RT. In polyploid cells, copy number is not uniform throughout the genome. Underreplication causes pericentric heterochromatin and defined regions of euchromatin to have reduced copy number relative to overall ploidy. SUUR and Rif1 are key regulators of underreplication, and Rif1 is a known regulator of replication timing (RT). Das et al. take a computational approach to measure replication timing in polyploid cells. Their results demonstrate that, while Rif1 and SUUR both promote underreplication, they differentially affect RT.
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