The TRESLIN-MTBP complex couples completion of DNA replication with S/G2 transition
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
Dokumenter
- Fulltext
Forlagets udgivne version, 7,04 MB, PDF-dokument
It has been proposed that ATR kinase senses the completion of DNA replication to initiate the S/G2 transition. In contrast to this model, we show here that the TRESLIN-MTBP complex prevents a premature entry into G2 from early S-phase independently of ATR/CHK1 kinases. TRESLIN-MTBP acts transiently at pre-replication complexes (preRCs) to initiate origin firing and is released after the subsequent recruitment of CDC45. This dynamic behavior of TRESLIN-MTBP implements a monitoring system that checks the activation of replication forks and senses the rate of origin firing to prevent the entry into G2. This system detects the decline in the number of origins of replication that naturally occurs in very late S, which is the signature that cells use to determine the completion of DNA replication and permit the S/G2 transition. Our work introduces TRESLIN-MTBP as a key player in cell-cycle control independent of canonical checkpoints.
| Originalsprog | Engelsk |
|---|---|
| Tidsskrift | Molecular Cell |
| Vol/bind | 82 |
| Udgave nummer | 18 |
| Sider (fra-til) | 3350-3365.e7 |
| Antal sider | 24 |
| ISSN | 1097-2765 |
| DOI | |
| Status | Udgivet - 2022 |
Bibliografisk note
Funding Information:
We thank Alexis Barr (Imperial College), Christopher Sansam (University of Oklahoma), and Niels Mailand (University of Copenhagen) for providing critical reagents. We thank Jiri Lukas, Ian Hickson, Julien Duxin (University of Copenhagen), and Kumar Somyajit (University of Southern Denmark) for revising and providing feedback on the manuscript. We thank David Willman with the assistance on immunoprecipitation studies and Justine Sitz for help with the confocal microscope. We thank everyone in the Toledo Laboratory for critical comments on the manuscript. Work at the Center for Chromosome Stability was supported by the European Research Council, European Union (ERC-StG-679754), and the Danish National Research Foundation, Denmark (DNRF115). Work at the University of Duisburg-Essen was supported by the NRW Rückkehrerförderprogramm fellowship. Work at the Novo Nordisk Foundation Center for Protein Research was supported by the Novo Nordisk Foundation (grant agreements NNF14CC0001 and NNF15CC0001). G.Z. performed the experiments. G.Z. and L.T. designed and analyzed the experiments. R.V. and E.M.-D. developed reagents and provided input for the study. S.A. and J.B. carried out initial experiments. D.B. provided critical reagents, input, and advice during the study. F.C. and A.M. carried out mass spectrometry analysis. M.L. analyzed the RNA-seq dataset. L.T. conceived, designed, and supervised the study. L.T. G.Z. and R.V. wrote the manuscript. All of the authors read, edited, and commented on the manuscript. The authors declare no competing interests. While citing references scientifically relevant for this work, we also actively worked to promote gender balance in our reference list.
Funding Information:
We thank Alexis Barr (Imperial College), Christopher Sansam (University of Oklahoma), and Niels Mailand (University of Copenhagen) for providing critical reagents. We thank Jiri Lukas, Ian Hickson, Julien Duxin (University of Copenhagen), and Kumar Somyajit (University of Southern Denmark) for revising and providing feedback on the manuscript. We thank David Willman with the assistance on immunoprecipitation studies and Justine Sitz for help with the confocal microscope. We thank everyone in the Toledo Laboratory for critical comments on the manuscript. Work at the Center for Chromosome Stability was supported by the European Research Council , European Union ( ERC-StG-679754 ), and the Danish National Research Foundation , Denmark ( DNRF115 ). Work at the University of Duisburg-Essen was supported by the NRW Rückkehrerförderprogramm fellowship. Work at the Novo Nordisk Foundation Center for Protein Research was supported by the Novo Nordisk Foundation (grant agreements NNF14CC0001 and NNF15CC0001 ).
Publisher Copyright:
© 2022 The Authors
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 321473826