Chaillot Julien, Cook Michael A, Corbeil Jacques, Sellam Adnane
Infectious Diseases Research Centre, Centre Hospitalier Universitaire (CHU) de Québec Research Center, Université Laval, Quebec City, Quebec, Canada.
Centre for Systems Biology, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, G1V 4G2 Canada.
G3 (Bethesda). 2017 Feb 9;7(2):355-360. doi: 10.1534/g3.116.037986.
One of the most critical but still poorly understood aspects of eukaryotic cell proliferation is the basis for commitment to cell division in late G1 phase, called Start in yeast and the Restriction Point in metazoans. In all species, a critical cell size threshold coordinates cell growth with cell division and thereby establishes a homeostatic cell size. While a comprehensive survey of cell size genetic determinism has been performed in the saprophytic yeasts and , very little is known in pathogenic fungi. As a number of critical Start regulators are haploinsufficient for cell size, we applied a quantitative analysis of the size phenome, using elutriation-barcode sequencing methodology, to 5639 barcoded heterozygous deletion strains of the opportunistic yeast Our screen identified conserved known regulators and biological processes required to maintain size homeostasis in the opportunistic yeast We also identified novel -specific size genes and provided a conceptual framework for future mechanistic studies. Interestingly, some of the size genes identified were required for fungal pathogenicity suggesting that cell size homeostasis may be elemental to fitness or virulence inside the host.
真核细胞增殖中最关键但仍了解甚少的一个方面是在G1期后期进入细胞分裂的基础，在酵母中称为起始点（Start），在后生动物中称为限制点（Restriction Point）。在所有物种中，一个关键的细胞大小阈值协调细胞生长与细胞分裂，从而建立一个稳态的细胞大小。虽然已经在腐生酵母中对细胞大小的遗传决定因素进行了全面调查，但对致病真菌的了解却很少。由于许多关键的起始调节因子对于细胞大小是单倍体不足的，我们使用淘析-条形码测序方法对机会性酵母的5639个条形码杂合缺失菌株进行了大小表型组的定量分析。我们的筛选确定了机会性酵母中维持大小稳态所需的保守的已知调节因子和生物学过程。我们还鉴定了新的特定大小基因，并为未来的机制研究提供了一个概念框架。有趣的是，一些鉴定出的大小基因是真菌致病性所必需的，这表明细胞大小稳态可能是宿主内适应性或毒力的基础。
