Rif1 Functions in a Tissue-Specific Manner To Control Replication Timing Through Its PP1-Binding Motif.

Autor:	Armstrong RL; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599., Das S; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37232., Hill CA; Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599., Duronio RJ; Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina 27599 duronio@med.unc.edu jared.nordman@vanderbilt.edu.; Integrative Program for Biological and Genome Sciences, University of North Carolina, Chapel Hill, North Carolina 27599.; Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599.; Department of Biology, University of North Carolina, Chapel Hill, North Carolina 27599.; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599., Nordman JT; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37232 duronio@med.unc.edu jared.nordman@vanderbilt.edu.
Jazyk:	angličtina
Zdroj:	Genetics [Genetics] 2020 May; Vol. 215 (1), pp. 75-87. Date of Electronic Publication: 2020 Mar 06.
DOI:	10.1534/genetics.120.303155
Abstrakt:	Replication initiation in eukaryotic cells occurs asynchronously throughout S phase, yielding early- and late-replicating regions of the genome, a process known as replication timing (RT). RT changes during development to ensure accurate genome duplication and maintain genome stability. To understand the relative contributions that cell lineage, cell cycle, and replication initiation regulators have on RT, we utilized the powerful developmental systems available in Drosophila melanogaster We generated and compared RT profiles from mitotic cells of different tissues and from mitotic and endocycling cells of the same tissue. Our results demonstrate that cell lineage has the largest effect on RT, whereas switching from a mitotic to an endoreplicative cell cycle has little to no effect on RT. Additionally, we demonstrate that the RT differences we observed in all cases are largely independent of transcriptional differences. We also employed a genetic approach in these same cell types to understand the relative contribution the eukaryotic RT control factor, Rif1, has on RT control. Our results demonstrate that Rif1 can function in a tissue-specific manner to control RT. Importantly, the Protein Phosphatase 1 (PP1) binding motif of Rif1 is essential for Rif1 to regulate RT. Together, our data support a model in which the RT program is primarily driven by cell lineage and is further refined by Rif1/PP1 to ultimately generate tissue-specific RT programs. (Copyright © 2020 Armstrong et al.)
Databáze:	MEDLINE
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