Ahmad Fouzia, Kaplan Craig D, Stewart Elspeth
School of Biological Sciences, University of Manchester, Manchester, UK.
Yeast. 2002 Dec;19(16):1381-98. doi: 10.1002/yea.917.
The RecQ-related family of DNA helicases is required for the maintenance of genomic stability in organisms ranging from bacteria to humans. In humans, mutation of three RecQ-related helicases, BLM, WRN and RecQL4, cause the cancer-prone and premature ageing diseases of Bloom syndrome, Werner's syndrome and Rothmund-Thompson syndrome, respectively. In the fission yeast Schizosaccharomyces pombe, disruption of the rqh1(+) gene, which encodes the single Sz. pombe RecQ-related helicase, causes cells to display reduced viability and elevated levels of chromosome loss. After S-phase arrest or DNA damage, cells lacking rqh1(+) function display elevated levels of homologous recombination and defective chromosome segregation. Here we show that, like other RecQ family members, the Rqh1p protein displays 3' to 5' DNA helicase activity. Interestingly, however, unlike other RecQ family members, the helicase activity of Rqh1p is only partially required for its function in recovery from S-phase arrest or DNA damage. We also report that high cellular levels of Rqh1p result in lethal chromosome segregation defects, while more moderate levels of Rqh1p cause significantly elevated rates of chromosome loss. This suggests that careful regulation of RecQ-like protein levels in eukaryotic cells is vital for maintaining genome stability.
从细菌到人类的各种生物体中,维持基因组稳定性都需要DNA解旋酶的RecQ相关家族。在人类中,三种RecQ相关解旋酶BLM、WRN和RecQL4发生突变,分别导致易患癌症和早衰的布卢姆综合征、沃纳综合征和罗思蒙德-汤姆森综合征。在裂殖酵母粟酒裂殖酵母中,编码单一粟酒裂殖酵母RecQ相关解旋酶的rqh1(+)基因被破坏,会导致细胞活力降低和染色体丢失水平升高。在S期停滞或DNA损伤后,缺乏rqh1(+)功能的细胞会出现同源重组水平升高和染色体分离缺陷。我们在此表明,与其他RecQ家族成员一样,Rqh1p蛋白具有3'到5'的DNA解旋酶活性。然而,有趣的是,与其他RecQ家族成员不同,Rqh1p的解旋酶活性在其从S期停滞或DNA损伤中恢复的功能中仅部分需要。我们还报告说,细胞内高水平的Rqh1p会导致致命的染色体分离缺陷,而中等水平的Rqh1p会导致染色体丢失率显著升高。这表明真核细胞中RecQ样蛋白水平的精确调控对于维持基因组稳定性至关重要。