Phase separation by ssDNA binding protein controlled via protein-protein and protein-DNA interactions.
Gábor M HaramiZoltán J KovácsRita PancsaJános PálinkásVeronika BaráthKrisztián TárnokAndrás Málnási-CsizmadiaMihály KovácsPublished in: Proceedings of the National Academy of Sciences of the United States of America (2020)
Bacterial single-stranded (ss)DNA-binding proteins (SSB) are essential for the replication and maintenance of the genome. SSBs share a conserved ssDNA-binding domain, a less conserved intrinsically disordered linker (IDL), and a highly conserved C-terminal peptide (CTP) motif that mediates a wide array of protein-protein interactions with DNA-metabolizing proteins. Here we show that the Escherichia coli SSB protein forms liquid-liquid phase-separated condensates in cellular-like conditions through multifaceted interactions involving all structural regions of the protein. SSB, ssDNA, and SSB-interacting molecules are highly concentrated within the condensates, whereas phase separation is overall regulated by the stoichiometry of SSB and ssDNA. Together with recent results on subcellular SSB localization patterns, our results point to a conserved mechanism by which bacterial cells store a pool of SSB and SSB-interacting proteins. Dynamic phase separation enables rapid mobilization of this protein pool to protect exposed ssDNA and repair genomic loci affected by DNA damage.
Keyphrases
- protein protein
- small molecule
- binding protein
- escherichia coli
- dna damage
- transcription factor
- circulating tumor
- single molecule
- oxidative stress
- induced apoptosis
- genome wide
- gene expression
- nucleic acid
- high resolution
- endoplasmic reticulum stress
- protein kinase
- cystic fibrosis
- cell proliferation
- klebsiella pneumoniae
- dna methylation
- cell death
- dna repair
- candida albicans
- biofilm formation