Daniel Jacques
Centre de Génétique Moléculaire, Centre National de la Recherche Scientifique, rue de la Terrasse, 91198, Gif-sur-Yvette, France.
Mol Genet Genomics. 2005 Dec;274(5):539-47. doi: 10.1007/s00438-005-0040-5. Epub 2005 Oct 1.
Using a new genetic selection approach in yeast termed fitness-based interferential genetics (FIG), genes that are in an antagonistic relationship with the Sir complexes were selected. Many of the functionally well-defined genes belong to various aging processes occurring in this organism. Three genes are somehow involved in glucose utilization (HXT4,YIL107c, EMI2). Another gene, CDC25, encodes the main regulator of the cyclic AMP pathway in response to glucose. STM1 has been implicated in the control of apoptosis, and indeed, this work shows that disruption of this gene results, among other phenotypes, in resistance to aging. LCB4, encoding a sphingoid bases kinase is linked to the cell integrity pathway. Two other genes, FHL1 and PEP5, are involved in the control of ribosome formation and vacuole biogenesis, respectively; and five genes, presently having unknown functions, could be new potentially interesting candidates for further studies in relation to yeast replicative aging. It is proposed that most, if not all, selected genes are downregulated by the Sir complexes. In addition to changing our view of the mechanisms used by the Sir complexes for extending life span in yeast, these findings could contribute to a better understanding of the role of the Sir complexes in the higher eukaryotes.
利用酵母中一种名为基于适应性的干扰遗传学（FIG）的新基因选择方法，筛选出了与Sir复合物呈拮抗关系的基因。许多功能明确的基因属于该生物体中发生的各种衰老过程。三个基因在某种程度上参与葡萄糖利用（HXT4、YIL107c、EMI2）。另一个基因CDC25编码响应葡萄糖的环磷酸腺苷途径的主要调节因子。STM1已被证明与细胞凋亡控制有关，实际上，这项研究表明，该基因的破坏除了导致其他表型外，还会导致抗老化。编码鞘氨醇碱基激酶的LCB4与细胞完整性途径相关。另外两个基因FHL1和PEP5分别参与核糖体形成和液泡生物发生的控制；还有五个功能未知的基因，可能是与酵母复制性衰老相关的进一步研究中潜在的有趣候选基因。有人提出，大多数（如果不是全部）选定的基因会被Sir复合物下调。这些发现不仅改变了我们对Sir复合物在酵母中延长寿命所使用机制的看法，还可能有助于更好地理解Sir复合物在高等真核生物中的作用。
