A novel family of TRF (DNA topoisomerase l-related function) genes required for proper nuclear segregation
A novel family of TRF (DNA topoisomerase l-related function) genes required for proper nuclear segregation
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DOI：
10.1093/nar/24.12.2404
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发表时间：
1996-06-15
影响因子：
14.9
通讯作者：
Christman, MF
中科院分区：
文献类型：
--
作者：
Castano, IB;HeathPagliuso, S;Christman, MF
我们最近报道了一个基因的鉴定，TRF 4（远DNA拓扑异构酶相关的功能），在筛选与DNA拓扑异构酶1（top1）中的突变一起合成致死的突变中，在此，我们描述了TRF 4基因家族的第二个成员TRF 5的分离。TRF 5的过表达补充了top1 trf 4双突变体的失活，预测的Trf 5蛋白与Trf 4p有55%的相同性和72%的相似性。与Trf 4p一样，Trf 5 p的一个区域与Top1 p的催化性转录酶N-末端同源，TRF 4/5功能是必需的，因为trf 4 trf 5双突变体是不可活的，一个trf 4（ts）trf 5双突变体在半容许温度下对抗微管剂噻苯咪唑超敏感，表明TRF 4/5功能在有丝分裂时是必需的。在限制性温度下检查trf 4（ts）trf 5突变体的核形态显示存在许多经历异常核分裂的细胞，以及许多无核细胞，证明TRF 4/5功能是适当有丝分裂所需的。数据库搜索显示可能存在粟酒裂殖酵母和Trf 4p的人类同源物，表明TRF 4是进化上高度保守的基因家族的典型成员。
We recently reported the identification of a gene, TRF4 (far DNA topoisomerase related function), in a screen for mutations that are synthetically lethal with mutations in DNA topoisomerase 1 (top1), Here we describe the isolation of a second member of the TRF4 gene family, TRF5, Overexpression of TRF5 complements the inviability of top1 trf4 double mutants, the predicted Trf5 protein is 55% identical and 72% similar to Trf4p. As with Trf4p, a region of Trf5p is homologous to the catalytically dispensable N-terminus of Top1p, The TRF4/5 function is essential as trf4 trf5 double mutants are inviable, A trf4 (ts) trf5 double mutant is hypersensitive to the anti-microtubule agent thiabendazole at a semi-permissive temperature, suggesting that TRF4/5 function is required at the time of mitosis. Examination of nuclear morphology in a trf4 (ts) trf5 mutant at a restrictive temperature reveals the presence of many cells undergoing aberrant nuclear division, as well as many anucleate cells, demonstrating that the TRF4/5 function is required for proper mitosis, Database searches reveal the existence of probable Schizosaccharomyces pombe and human homologs of Trf4p, indicating that TRF4 is the canonical member of a gene family that is highly conserved evolutionarily.