Fission yeast Stn1 maintains stability of repetitive DNA at subtelomere and ribosomal DNA regions.

Fission yeast Stn1 maintains stability of repetitive DNA at subtelomere and ribosomal DNA regions.
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DOI:
10.1093/nar/gkab767
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发表时间:
2021-10-11
影响因子:
14.9
通讯作者:
Ishikawa F
Ishikawa F
中科院分区:
生物学2区
文献类型:
--
作者:
Yamamoto I;Nakaoka H;Takikawa M;Tashiro S;Kanoh J;Miyoshi T;Ishikawa F

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端粒结合蛋白Stn 1在芽殖酵母和哺乳动物中形成CST(Cdc 13/CTC 1-STN 1-TEN 1)复合物。同样,裂变酵母Stn 1和Ten 1形成了端粒保护不可或缺的复合体。我们以前曾报道,stn 1 -1,高温敏感的突变体,迅速失去端粒DNA在限制性温度由于频繁失败的复制叉进展在端粒和亚端粒,都含有重复序列。然而,目前还不清楚Stn 1是否是维持其他重复DNA如核糖体DNA所必需的。在这项研究中,我们已经证明,stn 1 -1细胞,即使在允许的温度下生长,表现出动态重排的端粒近端区域的亚端粒和核糖体DNA重复序列。此外,在stn 1 -1突变体中观察到Rad 52和γ H2 A积累在核糖体DNA重复序列中。Stn 1 -1等位基因表现出的表型在Reb 1(一种复制叉屏障形成蛋白)不存在的情况下受到很大程度的抑制,这表明Stn 1参与了被逮捕的复制叉的维持。总的来说,我们建议Stn 1维持在亚端粒和rDNA区域的重复DNA的稳定性。
Telomere binding protein Stn1 forms the CST (Cdc13/CTC1-STN1-TEN1) complex in budding yeast and mammals. Likewise, fission yeast Stn1 and Ten1 form a complex indispensable for telomere protection. We have previously reported that stn1-1, a high-temperature sensitive mutant, rapidly loses telomere DNA at the restrictive temperature due to frequent failure of replication fork progression at telomeres and subtelomeres, both containing repetitive sequences. It is unclear, however, whether Stn1 is required for maintaining other repetitive DNAs such as ribosomal DNA. In this study, we have demonstrated that stn1-1 cells, even when grown at the permissive temperature, exhibited dynamic rearrangements in the telomere-proximal regions of subtelomere and ribosomal DNA repeats. Furthermore, Rad52 and γH2A accumulation was observed at ribosomal DNA repeats in the stn1-1 mutant. The phenotypes exhibited by the stn1-1 allele were largely suppressed in the absence of Reb1, a replication fork barrier-forming protein, suggesting that Stn1 is involved in the maintenance of the arrested replication forks. Collectively, we propose that Stn1 maintains the stability of repetitive DNAs at subtelomeres and rDNA regions.
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