Regulation of fragile sites expression in budding yeast by MEC1, RRM3 and hydroxyurea
Regulation of fragile sites expression in budding yeast by MEC1, RRM3 and hydroxyurea
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DOI：
10.1242/jcs.077313
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发表时间：
2011-01-15
影响因子：
4
通讯作者：
Cha, Rita S.
中科院分区：
文献类型：
--
作者：
Hashash, Nadia;Johnson, Anthony L.;Cha, Rita S.
脆性位点是基因组内表现出增加的染色体断裂倾向的特定位点。它们在哺乳动物中是保守的，也在低等真核生物中发现，包括酵母和苍蝇。许多条件，包括突变和外源因素，有助于脆性位点的表达，但它们之间的相互作用的性质仍然难以捉摸。在这里，我们研究了这一点，通过检查rrm 3三角洲，mec 1和羟基脲（HU），三个条件，诱导脆弱的网站，复制慢区（RSZ），一种类型的脆弱的网站在芽殖酵母的表达的综合影响。相反的预期，每个因素将有助于以独立的方式脆性位点的表达，我们表明，rrm 3三角洲和高浓度的胡抑制RSZ在mec 1 - 4 ts细胞的表达。进一步的分析表明，rrm 3德尔塔抑制发生通过促进Sml 1降解，而HU抑制RSZ通过过早的承诺，以不活力。综上所述，这些观察结果表明：（1）酵母基因组包含不同类型的脆性位点，涉及其表达的调节，以及（2）每种脆性位点诱导条件并不独立起作用，但可以引发细胞反应，该反应可以矛盾地阻止特定类型的脆性位点的表达。
Fragile sites are specific loci within the genome that exhibit increased tendencies for chromosome breakage. They are conserved among mammals and are also found in lower eukaryotes including yeast and fly. Many conditions, including mutations and exogenous factors, contribute to fragile site expression, but the nature of interaction among them remains elusive. Here, we investigated this by examining the combined effects of rrm3 Delta, mec1 and hydroxyurea (HU), three conditions that induce fragile sites, on expression of the replication slow zone (RSZ), a type of fragile site in budding yeast. Contrary to the expectation that each factor would contribute to fragile site expression in an independent manner, we show that rrm3 Delta and high concentrations of HU suppressed RSZ expression in mec1-4ts cells. Further analyses revealed that rrm3 Delta suppression occurs via promotion of Sml1 degradation, whereas HU suppresses RSZ via a premature commitment to inviability. Taken together, these observations demonstrate that: (1) the yeast genome contains different types of fragile site with regard to regulation of their expression, and (2) each fragile-site-inducing condition does not act independently, but can elicit a cellular response(s) that can paradoxically prevent the expression of a specific type(s) of fragile sites.