Nucleolar GTPase Bms1 displaces Ttf1 from RFB-sites to balance progression of rDNA transcription and replication.
Nucleolar GTPase Bms1 displaces Ttf1 from RFB-sites to balance progression of rDNA transcription and replication.
复制标题
核仁GTPase Bms1取代rfb位点上的Ttf1，以平衡rDNA转录和复制的进展。
DOI：
10.1093/jmcb/mjab074
复制
发表时间：
2022-01-29
影响因子：
5.5
通讯作者：
Peng J
中科院分区：
文献类型：
--
作者：
Zhu Y;Wang Y;Tao B;Han J;Chen H;Zhu Q;Huang L;He Y;Hong J;Li Y;Chen J;Huang J;Lo LJ;Peng J
18S、5.8S和28S核糖体RNA （rrna）通过RNA聚合酶I从rDNA共转录为前核糖体RNA (pre-rRNA)，其活性在s期旺盛，导致与rDNA复制冲突。这种冲突部分由rDNA下游的复制叉屏障（RFB）位点序列和RFB结合蛋白（如Ttf1）来解决。然而，Ttf1如何从rfb位点转移以允许复制分叉进展仍然是一个谜。在这里，我们报道了核核GTPase Bms1l的功能丧失，上调rDNA转录，导致复制叉停滞，并阻止细胞周期在s到g2的转变；然而，g1到s的转变是组成活跃的特征是持续的DNA合成。与此同时，标记rDNA转录的ubf、tif-IA和taf1b，标记dna损伤应答的Chk2、Rad51和p53，以及标记复制分叉失速的Rpa2、PCNA、Fen1和Ttf1在bms11突变体中都高度升高。我们发现Bms1除了与rc1相互作用外，还与Ttf1相互作用。最后，我们通过染色质免疫沉淀测序确定了斑马鱼Ttf1的rfb位点，并发现Bms1通过其GTPase活性将Ttf1 - rfb复合物解离。我们认为Bms1分别通过与Rcl1和Ttf1的相互作用来平衡rDNA在s期的转录和复制。TTF1和Bms1一起可能在rDNA位点上施加s期检查点。
18S, 5.8S, and 28S ribosomal RNAs (rRNAs) are cotranscribed as a pre-ribosomal RNA (pre-rRNA) from the rDNA by RNA polymerase I whose activity is vigorous during the S-phase, leading to a conflict with rDNA replication. This conflict is resolved partly by replication-fork-barrier (RFB)-sites sequences located downstream of the rDNA and RFB-binding proteins such as Ttf1. However, how Ttf1 is displaced from RFB-sites to allow replication fork progression remains elusive. Here, we reported that loss-of-function of Bms1l, a nucleolar GTPase, upregulates rDNA transcription, causes replication-fork stall, and arrests cell cycle at the S-to-G2 transition; however, the G1-to-S transition is constitutively active characterized by persisting DNA synthesis. Concomitantly, ubf, tif-IA, and taf1b marking rDNA transcription, Chk2, Rad51, and p53 marking DNA-damage response, and Rpa2, PCNA, Fen1, and Ttf1 marking replication fork stall are all highly elevated in bms1l mutants. We found that Bms1 interacts with Ttf1 in addition to Rc1l. Finally, we identified RFB-sites for zebrafish Ttf1 through chromatin immunoprecipitation sequencing and showed that Bms1 disassociates the Ttf1‒RFB complex with its GTPase activity. We propose that Bms1 functions to balance rDNA transcription and replication at the S-phase through interaction with Rcl1 and Ttf1, respectively. TTF1 and Bms1 together might impose an S-phase checkpoint at the rDNA loci.
登录
查看更多内容
影响因子：
7.3
作者：
Henras, Anthony K.;Plisson-Chastang, Celia;O'Donohue, Marie-Francoise;Chakraborty, Anirban;Gleizes, Pierre-Emmanuel
通讯作者：
Gleizes, Pierre-Emmanuel
影响因子：
5.3
作者：
Akamatsu, Yufuko;Kobayashi, Takehiko
通讯作者：
Kobayashi, Takehiko
p53 内含子 4 中自然发生的 4-bp 缺失产生了一系列具有抗凋亡功能的新型 p53 亚型
影响因子：
14.9
作者：
Shi H;Tao T;Huang D;Ou Z;Chen J;Peng J
通讯作者：
Peng J
影响因子：
64.5
作者：
Engel, Christoph;Gubbey, Tobias;Cramer, Patrick
通讯作者：
Cramer, Patrick
影响因子：
11.4
作者：
Billy, E;Wegierski, T;Filipowicz, W
通讯作者：
Filipowicz, W