Fission yeast Taz1 and RPA are synergistically required to prevent rapid telomere loss
Fission yeast Taz1 and RPA are synergistically required to prevent rapid telomere loss
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DOI：
10.1091/mbc.e06-12-1084
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发表时间：
2007-06-01
影响因子：
3.3
通讯作者：
Ueno, Masaru
中科院分区：
文献类型：
--
作者：
Kibe, Tatsuya;Ono, Yuuki;Ueno, Masaru
端粒复合体必须允许核酸酶和解旋酶处理染色体末端，使其成为端粒酶的底物，同时防止这些相同的活动破坏染色体末端保护。复制蛋白A（RPA）与单链DNA结合，是DNA复制、重组、修复和端粒维持所必需的。在分裂酵母中，端粒结合蛋白Taz 1保护端粒并负调节端粒酶。在这里，我们表明，taz 1-d rad 11-D223 Y双突变体失去了端粒DNA，这表明RPA（Rad 11）和Taz 1是协同需要防止端粒损失。端粒损失的taz 1-d rad 11-D223 Y双突变体被抑制的RecQ解旋酶（Rqh 1）的解旋酶结构域的额外突变，或过表达的Pot 1，单链端粒结合蛋白，是必不可少的保护染色体末端。从我们的研究结果中，我们提出，在没有Taz 1和功能RPA，Pot 1不能正常工作和解旋酶活性的Rqh 1促进端粒损失。我们的研究结果表明，控制端粒Rqh 1的活性对于预防基因组不稳定性至关重要。
The telomere complex must allow nucleases and helicases to process chromosome ends to make them substrates for telomerase, while preventing these same activities from disrupting chromosome end-protection. Replication protein A (RPA) binds to single-stranded DNA and is required for DNA replication, recombination, repair, and telomere maintenance. In fission yeast, the telomere binding protein Taz1 protects telomeres and negatively regulates telomerase. Here, we show that taz1-d rad11-D223Y double mutants lose their telomeric DNA, indicating that RPA (Rad11) and Taz1 are synergistically required to prevent telomere loss. Telomere loss in the taz1-d rad11-D223Y double mutants was suppressed by additional mutation of the helicase domain in a RecQ helicase (Rqh1), or by overexpression of Pot1, a single-strand telomere binding protein that is essential for protection of chromosome ends. From our results, we propose that in the absence of Taz1 and functional RPA, Pot1 cannot function properly and the helicase activity of Rqh1 promotes telomere loss. Our results suggest that controlling the activity of Rqh1 at telomeres is critical for the prevention of genomic instability.