4.5 Article

The Spt7 subunit of the SAGA complex is required for the regulation of lifespan in both dividing and nondividing yeast cells

Journal

MECHANISMS OF AGEING AND DEVELOPMENT
Volume 196, Issue -, Pages -

Publisher

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mad.2021.111480

Keywords

Spt7; SAGA; Lifespan; DNA recombination; Aging

Funding

  1. National Research Foundation of Korea (NRF) - South Korean government [NRF-2016R1A2B2008217]

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The Spt7 subunit of the SAGA complex plays a crucial role in regulating the replicative and chronological lifespan of yeast cells by controlling DNA recombination rate and overall mRNA expression. Its loss leads to increased DNA recombination frequency and spontaneous Rad52 foci, suggesting a role in maintaining genomic stability and lifespan regulation in eukaryotes.
Spt7 belongs to the suppressor of Ty (SPT) module of the Spt-Ada-Gcn5-acetyltransferase (SAGA) complex and is known as the yeast ortholog of human STAF65 gamma. Spt7 lacks intrinsic enzymatic activity but is responsible for the integrity and proper assembly of the SAGA complex. Here, we determined the role of the SAGA Spt7 subunit in cellular aging. We found that Spt7 was indispensable for a normal lifespan in both dividing and nondividing yeast cells. In the quiescent state of cells, Spt7 was required for the control of overall mRNA levels. In mitotically active cells, deletion of the SPT module had little effect on the recombination rate within heterochromatic ribosomal DNA (rDNA) loci, but loss of Spt7 profoundly elevated the plasmid-based DNA recombination frequency. Consistently, loss of Spt7 increased spontaneous Rad52 foci by approximately two-fold upon entry into S phase. These results provide evidence that Spt7 contributes to the regulation of the normal replicative lifespan (RLS) and chronological lifespan (CLS), possibly by controlling the DNA recombination rate and overall mRNA expression. We propose that the regulation of SAGA complex integrity by Spt7 might be involved in the conserved regulatory pathway for lifespan regulation in eukaryotes.

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