Department of Molecular and Life Science, College of Science and Convergence Technology, Hanyang University ERICA Campus, Ansan 15588, Republic of Korea.
School of Life Sciences, BK21 Plus KNU Creative BioResearch Group, College of National Sciences, Kyungpook National University, Daegu 41566, Republic of Korea.
Mech Ageing Dev. 2021 Jun;196:111480. doi: 10.1016/j.mad.2021.111480. Epub 2021 Apr 5.
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 STAF65γ. 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.
Spt7 属于 Spt-Ada-Gcn5-乙酰转移酶（SAGA）复合物的 Ty 抑制物（SPT）模块，是酵母中人类 STAF65γ 的同源物。Spt7 缺乏内在的酶活性，但负责 SAGA 复合物的完整性和正确组装。在这里，我们确定了 SAGA Spt7 亚基在细胞衰老中的作用。我们发现 Spt7 在有丝分裂和非有丝分裂酵母细胞的正常寿命中都是必不可少的。在细胞的静止状态下，Spt7 对于控制总 mRNA 水平是必需的。在有丝分裂活跃的细胞中，缺失 SPT 模块对异染色质核糖体 DNA（rDNA）基因座内的重组率几乎没有影响，但缺失 Spt7 会显著提高基于质粒的 DNA 重组频率。一致地，缺失 Spt7 会使 Rad52 焦点在进入 S 期时增加约两倍。这些结果表明 Spt7 有助于调节正常的复制寿命（RLS）和时序寿命（CLS），可能是通过控制 DNA 重组率和总 mRNA 表达。我们提出，Spt7 对 SAGA 复合物完整性的调节可能参与了真核生物寿命调节的保守调控途径。
