Two closely related RecQ helicases have antagonistic roles in homologous recombination and DNA repair in Arabidopsis thaliana
Two closely related RecQ helicases have antagonistic roles in homologous recombination and DNA repair in Arabidopsis thaliana
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DOI：
10.1073/pnas.0705998104
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发表时间：
2007-11-20
影响因子：
11.1
通讯作者：
Puchta, Holger
中科院分区：
文献类型：
--
作者：
Hartung, Frank;Suer, Stefanie;Puchta, Holger
RecQ解旋酶参与所有生命王国中复制、重组和修复过程中产生的DNA结构的加工。不同RecQ同源物的突变导致严重的人类疾病，如布卢姆（BLM）或沃纳（WRN）综合征。RecQ功能的丧失通常伴随着由缺乏交叉抑制引起的过度重组。在拟南芥基因组中存在七个不同的RecQ基因。其中两个（AtRECQ4A和4B）是由于最近的重复而产生的，并且在蛋白质水平上仍然接近70%相同。这些基因的敲除导致拮抗表型：RECQ4A突变体显示出对DNA损伤剂的敏感性，增强的同源重组（HR）和mus81背景下的致死性。此外，RECQ4A的突变部分抑制AtTOP 3 α突变体的致死表型，这种现象以前仅在单细胞真核生物的RecQ同源物中得到证实。总之，这些事实有力地表明，在植物中RECQ4A在功能上等同于酿酒酵母的SGS1和哺乳动物BLM蛋白。与此形成鲜明对比的是，密切相关的RECQ4B的突变体对诱变剂不敏感，在mus81背景下不能存活，并且不能抑制由TOP3 α缺失引起的诱导致死性。此外，它们在HR中受到强烈损害。因此，AtRECQ4B是特别需要促进但不抑制交叉的，其作用不同于所有已知的真核RecQ同源物。
RecQ helicases are involved in the processing of DNA structures arising during replication, recombination, and repair throughout all kingdoms of life. Mutations of different RecQ homologues are responsible for severe human diseases, such as Blooms (BLM) or Werner (WRN) syndrome. The loss of RecQ function is often accompanied by hyperrecombination caused by a lack of crossover suppression. In the Arabidopsis genome seven different RecQ genes are present. Two of them (AtRECQ4A and 4B) arose because of a recent duplication and are still nearly 70% identical on a protein level. Knockout of these genes leads to antagonistic phenotypes: the RECQ4A mutant shows sensitivity to DNA-damaging agents, enhanced homologous recombination (HR) and lethality in a mus81 background. Moreover, mutation of RECQ4A partially suppresses the lethal phenotype of an AtTOP3 alpha mutant, a phenomenon that had previously been demonstrated for RecQ homologues of unicellular eukaryotes only. Together, these facts strongly suggest that in plants RECQ4A is functionally equivalent to SGS1 of Saccharomyces cerevisiae and the mammalian BLM protein. In stark contrast, mutants of the closely related RECQ4B are not mutagen-sensitive, not viable in a mus81 background, and unable to suppress the induced lethality caused by loss of TOP3 alpha. Moreover, they are strongly impaired in HR. Thus, AtRECQ4B is specifically required to promote but not to suppress crossovers, a role in which it differs from all eukaryotic RecQ homologues known.