Hofmann A F, Harris S D
Department of Microbiology, University of Connecticut Health Center, Farmington, Connecticut 06030-3205, USA.
Genetics. 2001 Dec;159(4):1595-604. doi: 10.1093/genetics/159.4.1595.
In Aspergillus nidulans, the uvsB gene encodes a member of the PI-3K-related kinase family of proteins. We have recently shown that UVSB is required for multiple aspects of the DNA damage response. Since the musN227 mutation is capable of partially suppressing defects caused by uvsB mutations, we sought to understand the mechanism underlying the suppression by cloning the musN gene. Here, we report that musN encodes a RecQ helicase with homology to S. pombe rqh1, S. cerevisiae sgs1, and human BLM and WRN. Phenotypic characterization of musN mutant alleles reveals that MUSN participates in the response to a variety of genotoxic agents. The slow growth and genotoxin sensitivity of a musN null mutant can be partially suppressed by a defect in homologous recombination caused by the uvsC114 mutation. In addition, we present evidence suggesting that MUSN may promote recovery from the DNA damage response. We suggest that a block to recovery caused by the musN227 mutation, coupled with the modest accumulation of recombination intermediates, can suppress defects caused by uvsB mutations. Finally, we report that another RecQ helicase, ORQA, performs a function that partially overlaps that of MUSN.
在构巢曲霉中,uvsB基因编码PI-3K相关蛋白激酶家族的一个成员。我们最近发现,DNA损伤反应的多个方面都需要UVSB。由于musN227突变能够部分抑制uvsB突变引起的缺陷,我们试图通过克隆musN基因来了解这种抑制作用的潜在机制。在此,我们报告musN编码一种RecQ解旋酶,与粟酒裂殖酵母的rqh1、酿酒酵母的sgs1以及人类的BLM和WRN具有同源性。musN突变等位基因的表型特征表明,MUSN参与对多种基因毒性剂的反应。uvsC114突变导致的同源重组缺陷可部分抑制musN缺失突变体的生长缓慢和对基因毒素的敏感性。此外,我们提供的证据表明,MUSN可能促进从DNA损伤反应中恢复。我们认为,musN227突变导致的恢复受阻,再加上重组中间体的适度积累,能够抑制uvsB突变引起的缺陷。最后,我们报告另一种RecQ解旋酶ORQA执行的功能与MUSN部分重叠。