PUBLICATION
Nucleolar GTPase Bms1 displaces Ttf1 from RFB-sites to balance progression of rDNA transcription and replication
- Authors
- 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, L.J., Peng, J.
- ID
- ZDB-PUB-211119-4
- Date
- 2021
- Source
- Journal of molecular cell biology 13(12): 902-917 (Journal)
- Registered Authors
- Chen, Jun, Peng, Jinrong
- Keywords
- Bms1, GTPase, Ttf1, cell cycle, nucleolus, rDNA, replication-fork barrier, ribosome small subunit processome, zebrafish
- Datasets
- GEO:GSE176455
- MeSH Terms
-
- Animals
- DNA Replication
- DNA, Ribosomal/genetics
- GTP Phosphohydrolases*/genetics
- GTP Phosphohydrolases*/metabolism
- RNA Polymerase I/metabolism
- RNA, Ribosomal/genetics
- Zebrafish*/genetics
- PubMed
- 34791311 Full text @ J. Mol. Cell Biol.
Citation
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, L.J., Peng, J. (2021) Nucleolar GTPase Bms1 displaces Ttf1 from RFB-sites to balance progression of rDNA transcription and replication. Journal of molecular cell biology. 13(12):902-917.
Abstract
18S, 5.8S, and 28S ribosomal RNAs (rRNAs) are co-transcribed 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 sequences (RFB-sites) 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping