Extragenic suppression and synthetic lethality among Chlamydomonas reinhardtii mutants resistant to anti-microtubule drugs.

Extragenic suppression and synthetic lethality among Chlamydomonas reinhardtii mutants resistant to anti-microtubule drugs.
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抗微管药物耐药的莱茵衣藻突变体的外源抑制和合成致死率。

DOI:
10.1093/genetics/122.3.567
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发表时间:
1989
期刊:
影响因子:
3.3
通讯作者:
Lefebvre,PA
Lefebvre,PA
中科院分区:
生物学2区
文献类型:
--
作者:
James,SW;Silflow,CD;Thompson,MD;Ranum,LP;Lefebvre,PA

文献摘要

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用抗微管剂氨磺灵(oryzalin,ORY)、秋水仙碱(colchicine,COL)和紫杉醇(taxol,TAX)筛选出3个条件致死(ts-)的隐性突变体,它们定义了两个新的必需基因座ory 1和cor 1。这两个ory 1突变体赋予的电阻ORY,TAX,COL; cor 1突变体赋予的电阻只COL。每个突变体显示野生型敏感性的一些无关的抑制剂。装配和拆卸中的ory 1突变体的鞭毛微管显示野生型的敏感性ORY和COL,这表明ory 1基因产物不参与这些过程或ory 1基因产物本身是不足以赋予抗性。ory 1位点定位于连锁群X; cor 1定位于连锁群XII的左臂。在ory 1和cor 1突变之间观察到合成致死相互作用,即,推断的Ory 1Cor 1双突变体在允许温度下是无活力的。ory 1 -1的条件致死表型被用来选择许多自发的TS+回复突变体,这在高频率出现。回复突变体的遗传和表型特征表明:(1)回复突变体分为四种表型类型,包括一些赋予ORY超敏感性的类型和另一些赋予冷敏感致死性的类型,(2)回复突变在大多数或所有情况下由基因外抑制子引起,(3)抑制子突变在杂合(sup/+)二倍体中表现出复杂的行为,(4)许多不同的基因座可能能够抑制ory 1突变体,和(5)ory 1 -1的抑制子有效地抑制独立分离的等位基因ory 1 -2。总之,ory 1,cor 1和抑制基因突变确定了一些相互作用的位点参与的基本细胞过程,特别是敏感的抗微管剂。
The antimicrotubule agents oryzalin (ORY), colchicine (COL) and taxol (TAX) were used to select three recessive, conditional lethal (ts-) mutants which defined two new essential loci, ory1 and cor1. The two ory1 mutants conferred resistance to ORY, TAX, and COL; the cor1 mutant conferred resistance only to COL. Each of the mutants displayed wild-type sensitivity to a number of unrelated inhibitors. Assembly and disassembly of flagellar microtubules in the ory1 mutants displayed wild-type sensitivity to ORY and COL, suggesting that the ory1 gene product either does not participate in these processes or the ory1 gene product alone is not sufficient to confer resistance. The ory1 locus mapped to linkage group X; cor1 was mapped to the left arm of linkage group XII. A synthetic lethal interaction was observed between ory1 and cor1 mutations, i.e., inferred ory1 cor1 double mutants were inviable at the permissive temperature. The conditional lethal phenotype of ory1-1 was used to select many spontaneous TS+ revertants, which arose at high frequencies. Genetic and phenotypic characterization of the revertants demonstrated that (1) the revertants fell into four phenotypic classes, including some which conferred supersensitivity to ORY and others which conferred cold-sensitive lethality, (2) reversion was caused in most or all cases by extragenic suppressors, (3) suppressor mutations displayed complex behavior in heterozygous (sup/+) diploids, (4) many different loci may be capable of suppressing ory1 mutants, and (5) suppressors of ory1-1 efficiently suppressed an independently isolated allele, ory1-2. Taken together the ory1, cor1, and suppressor mutations identify a number of interacting loci involved in essential cellular processes which are specifically susceptible to antimicrotubule agents.