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A common strategy for initiating the transition from proliferation to quiescence

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Abstract

Development, tissue renewal and long term survival of multi-cellular organisms is dependent upon the persistence of stem cells that are quiescent, but retain the capacity to re-enter the cell cycle to self-renew, or to produce progeny that can differentiate and re-populate the tissue. Deregulated release of these cells from the quiescent state, or preventing them from entering quiescence, results in uncontrolled proliferation and cancer. Conversely, loss of quiescent cells, or their failure to re-enter cell division, disrupts organ development and prevents tissue regeneration and repair. Understanding the quiescent state and how cells control the transitions in and out of this state is of fundamental importance. Investigations into the mechanics of G1 arrest during the transition to quiescence continue to identify striking parallels between the strategies used by yeast and mammals to regulate this transition. When cells commit to a stable but reversible arrest, the G1/S genes responsible for promoting S phase must be inhibited. This process, from yeast to humans, involves the formation of quiescence-specific complexes on their promoters. In higher cells, these so-called DREAM complexes of E2F4/DP/RBL/MuvB recruit the highly conserved histone deacetylase HDAC1, which leads to local histone deacetylation and repression of S phase-promoting transcripts. Quiescent yeast cells also show pervasive histone deacetylation by the HDAC1 counterpart Rpd3. In addition, these cells contain quiescence-specific regulators of G1/S genes: Msa1 and Msa2, which can be considered components of the yeast equivalent of the DREAM complex. Despite a lack of physical similarities, the goals and the strategies used to achieve a reversible transition to quiescence are highly conserved. This motivates a detailed study of this process in the simple model organism: budding yeast.

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Acknowledgments

We thank members of the Breeden lab for helpful comments on the manuscript. This work was supported by the National Institutes of Health, National Institute on Aging Grant R21-AG048595 to L. L. B.

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  1. Basic Sciences Division, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave N, Seattle, WA, 98109, USA

    Shawna Miles & Linda Breeden

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Correspondence to Linda Breeden.

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Communicated by M. Kupiec.

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Miles, S., Breeden, L. A common strategy for initiating the transition from proliferation to quiescence. Curr Genet 63, 179–186 (2017). https://doi.org/10.1007/s00294-016-0640-0

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