Replication timing analysis in polyploid cells reveals Rif1 uses multiple mechanisms to promote underreplication in Drosophila |
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| Authors: | Souradip Das Madison Caballero Tatyana Kolesnikova Igor Zhimulev Amnon Koren Jared Nordman |
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| Affiliation: | 1. Department of Biological Sciences, Vanderbilt University, Nashville, TN 37232, USA;2. Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853, USA;3. Institute of Molecular and Cellular Biology, Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia;4. Laboratory of Structural, Functional and Comparative Genomics, Novosibirsk State University, 630090 Novosibirsk, Russia |
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| Abstract: | 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. |
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| Keywords: | DNA replication common fragile sites replication timing Drosophila genome stability |
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