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Ssu72 磷酸酶是一种保守的端粒复制终止因子。

Ssu72 phosphatase is a conserved telomere replication terminator.

机构信息

Instituto Gulbenkian de Ciência, Oeiras, Portugal

Instituto Gulbenkian de Ciência, Oeiras, Portugal.

出版信息

EMBO J. 2019 Apr 1;38(7). doi: 10.15252/embj.2018100476. Epub 2019 Feb 21.

DOI:10.15252/embj.2018100476
PMID:30796050
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6443209/
Abstract

Telomeres, the protective ends of eukaryotic chromosomes, are replicated through concerted actions of conventional DNA polymerases and elongated by telomerase, but the regulation of this process is not fully understood. Telomere replication requires (Ctc1/Cdc13)-Stn1-Ten1, a telomeric ssDNA-binding complex homologous to RPA Here, we show that the evolutionarily conserved phosphatase Ssu72 is responsible for terminating the cycle of telomere replication in fission yeast. Ssu72 controls the recruitment of Stn1 to telomeres by regulating Stn1 phosphorylation at Ser74, a residue located within its conserved OB-fold domain. Consequently, mutants are defective in telomere replication and exhibit long 3'-ssDNA overhangs, indicative of defective lagging-strand DNA synthesis. We also show that hSSU72 regulates telomerase activation in human cells by controlling recruitment of hSTN1 to telomeres. These results reveal a previously unknown yet conserved role for the phosphatase SSU72, whereby this enzyme controls telomere homeostasis by activating lagging-strand DNA synthesis, thus terminating the cycle of telomere replication.

摘要

端粒是真核染色体的保护性末端，通过常规 DNA 聚合酶的协同作用进行复制，并通过端粒酶延伸，但这个过程的调控机制还不完全清楚。端粒复制需要（Ctc1/Cdc13）-Stn1-Ten1，这是一种与 RPA 同源的端粒 ssDNA 结合复合物。在这里，我们表明进化上保守的磷酸酶 Ssu72 负责终止裂殖酵母中端粒复制的循环。Ssu72 通过调节 Stn1 丝氨酸 74 位的磷酸化来控制 Stn1 向端粒的募集，该残基位于其保守的 OB 折叠结构域内。因此，突变体在端粒复制中存在缺陷，并表现出长的 3'-ssDNA 突出，表明滞后链 DNA 合成存在缺陷。我们还表明，hSSU72 通过控制 hSTN1 向端粒的募集来调节人细胞中端粒酶的激活。这些结果揭示了磷酸酶 SSU72 的一个以前未知但保守的作用，即该酶通过激活滞后链 DNA 合成来控制端粒稳态，从而终止端粒复制的循环。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/9f68c955e827/EMBJ-38-e100476-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/cb8d0bb5487a/EMBJ-38-e100476-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/5539ad18dbb8/EMBJ-38-e100476-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/f59bf6ff803e/EMBJ-38-e100476-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/cc846df94f9a/EMBJ-38-e100476-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/8bd389457fa7/EMBJ-38-e100476-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/ae546d660d1a/EMBJ-38-e100476-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/84f7aa17eda0/EMBJ-38-e100476-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/17a64ed49151/EMBJ-38-e100476-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/7e5185ea564d/EMBJ-38-e100476-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/9f68c955e827/EMBJ-38-e100476-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/cb8d0bb5487a/EMBJ-38-e100476-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/5539ad18dbb8/EMBJ-38-e100476-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/f59bf6ff803e/EMBJ-38-e100476-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/cc846df94f9a/EMBJ-38-e100476-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/8bd389457fa7/EMBJ-38-e100476-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/ae546d660d1a/EMBJ-38-e100476-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/84f7aa17eda0/EMBJ-38-e100476-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/17a64ed49151/EMBJ-38-e100476-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/7e5185ea564d/EMBJ-38-e100476-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f5f2/6443209/9f68c955e827/EMBJ-38-e100476-g009.jpg

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