@article{7e107a664c054ec690890cf747e30110,
title = "Cell division protein FtsK coordinates bacterial chromosome segregation and daughter cell separation in Staphylococcus aureus",
abstract = "Unregulated cell cycle progression may have lethal consequences and therefore, bacteria have various mechanisms in place for the precise spatiotemporal control of cell cycle events. We have uncovered a new link between chromosome replication/segregation and splitting of the division septum. We show that the DNA translocase domain-containing divisome protein FtsK regulates cellular levels of a peptidoglycan hydrolase Sle1, which is involved in cell separation in the bacterial pathogen Staphylococcus aureus. FtsK interacts with a chaperone (trigger factor, TF) and establishes a FtsK-dependent TF concentration gradient that is higher in the septal region. Trigger factor binds Sle1 and promotes its preferential export at the septal region, while also preventing Sle1 degradation by the ClpXP proteolytic machinery. Upon conditions that lead to paused septum synthesis, such as DNA damage or impaired DNA replication/segregation, TF gradient is dissipated and Sle1 levels are reduced, thus halting premature septum splitting.",
keywords = "bacterial cell cycle, chromosome replication and segregation, FtsK, peptidoglycan hydrolases, Staphylococcus aureus",
author = "Helena Veiga and Ambre Jousselin and Simon Sch{\"a}per and Saraiva, {Bruno M.} and Marques, {Leonor B.} and Patricia Reed and Joana Wilton and Pereira, {Pedro M.} and Filipe, {S{\'e}rgio R.} and Pinho, {Mariana G.}",
note = "Funding Information: We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center T{\"u}bingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC‐2017‐CoG‐771709 (to MGP), by national funds through FCT– Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia, PTDC/BIA‐MIC/6982/2020 (to HV); PTDC/BIA‐PLA/3432/2012 (to SRF); FCT through MOSTMICRO‐ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and FCT fellowship SFRH/BD/147052/2019 (to BMS); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska‐Curie grant agreement No 839596 (to SS) and by the European Molecular Biology Organization through award ALTF 673‐2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com . Funding Information: We thank Nathalie Reichmann and Leendert Hamoen (University of Amsterdam) for critical reading of the manuscript, Ana Velic (Proteome Center T{\"u}bingen) for help with proteome analysis and Mike VanNieuwenhze (Indiana University) for the generous gift of HADA. This study was funded by the European Research Council through grant ERC-2017-CoG-771709 (to MGP), by national funds through FCT– Funda{\c c}{\~a}o para a Ci{\^e}ncia e a Tecnologia, PTDC/BIA-MIC/6982/2020 (to HV); PTDC/BIA-PLA/3432/2012 (to SRF); FCT through MOSTMICRO-ITQB R&D Unit (UIDB/04612/2020, UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020) and FCT fellowship SFRH/BD/147052/2019 (to BMS); by the Swiss National National Foundation through P300P3_155346 (to AJ); by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 839596 (to SS) and by the European Molecular Biology Organization through award ALTF 673-2018 (to SS). Figure 6D and Appendix Fig S7 were created with Biorender.com. Publisher Copyright: {\textcopyright} 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.",
year = "2023",
month = jun,
day = "1",
doi = "10.15252/embj.2022112140",
language = "English",
volume = "42",
journal = "Embo Journal",
issn = "0261-4189",
publisher = "EMBO Press",
number = "11",
}