Watt P M, Hickson I D, Borts R H, Louis E J
Imperial Cancer Research Fund Laboratories, University of Oxford, John Radcliffe Hospital, United Kingdom.
Genetics. 1996 Nov;144(3):935-45. doi: 10.1093/genetics/144.3.935.
The Saccharomyces cerevisiae SGS1 gene is homologous to Escherichia coli RecQ and the human BLM and WRN proteins that are defective in the cancer-prone disorder Bloom's syndrome and the premature aging disorder Werner's syndrome, respectively. While recQ mutants are deficient in conjugational recombination and DNA repair, Bloom's syndrome cell lines show hyperrecombination. Bloom's and Werner's syndrome cell lines both exhibit chromosomal instability, sgs1 delta strains show mitotic hyperrecombination, as do Bloom's cells. This was manifested as an increase in the frequency of interchromosomal homologous recombination, intrachromosomal excision recombination, and ectopic recombination. Hyperrecombination was partially independent of both RAD52 and RAD1. Meiotic recombination was not increased in sgs1 delta mutants, although meiosis I chromosome missegregation has been shown to be elevated sgs1 delta suppresses the slow growth of a top3 delta strain lacking topoisomerase III. Although there was an increase in subtelomeric Y' instability in sgs1 delta strains due to hyperrecombination, no evidence was found for an increase in the instability of terminal telomeric sequences in a top3 delta or a sgs1 delta strain. This contrasts with the telomere maintenance defects of Werner's patients. We conclude that the SGS1 gene product is involved in the maintenance of genome stability in S. cerevisiae.
酿酒酵母SGS1基因与大肠杆菌RecQ以及人类BLM和WRN蛋白同源，后两者分别在易患癌症的布卢姆综合征和早衰性疾病沃纳综合征中存在缺陷。虽然recQ突变体在接合重组和DNA修复方面存在缺陷，但布卢姆综合征细胞系表现出超重组。布卢姆综合征和沃纳综合征细胞系均表现出染色体不稳定，sgs1Δ菌株表现出有丝分裂超重组，布卢姆综合征细胞也是如此。这表现为染色体间同源重组、染色体内切除重组和异位重组频率的增加。超重组部分独立于RAD52和RAD1。sgs1Δ突变体的减数分裂重组没有增加，尽管已证明减数分裂I染色体错分离在sgs1Δ中升高，sgs1Δ抑制了缺乏拓扑异构酶III的top3Δ菌株的缓慢生长。虽然由于超重组，sgs1Δ菌株的亚端粒Y'不稳定性增加，但在top3Δ或sgs1Δ菌株中未发现端粒末端序列不稳定性增加的证据。这与沃纳综合征患者的端粒维持缺陷形成对比。我们得出结论，SGS1基因产物参与酿酒酵母基因组稳定性的维持。
