DNA packaging by molecular motors: from bacteriophage to human chromosomes

Prevo, Bram; Earnshaw, William C.

doi:10.1038/s41576-024-00740-y

Cited by 3 publications

References 188 publications

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Near millimolar concentration of nucleosomes in mitotic chromosomes from late prometaphase into anaphase

Cisneros-Soberanis,

Simpson,

Beckett

et al. 2024

Journal of Cell Biology

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Chromosome compaction is a key feature of mitosis and critical for accurate chromosome segregation. However, a precise quantitative analysis of chromosome geometry during mitotic progression is lacking. Here, we use volume electron microscopy to map, with nanometer precision, chromosomes from prometaphase through telophase in human RPE1 cells. During prometaphase, chromosomes acquire a smoother surface, their arms shorten, and the primary centromeric constriction is formed. The chromatin is progressively compacted, ultimately reaching a remarkable nucleosome concentration of over 750 µM in late prometaphase that remains relatively constant during metaphase and early anaphase. Surprisingly, chromosomes then increase their volume in late anaphase prior to deposition of the nuclear envelope. The plateau of total chromosome volume from late prometaphase through early anaphase described here is consistent with proposals that the final stages of chromatin condensation in mitosis involve a limit density, such as might be expected for a process involving phase separation.

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Near millimolar concentration of nucleosomes in mitotic chromosomes from late prometaphase into anaphase

Cisneros-Soberanis,

Simpson,

Beckett

et al. 2024

Journal of Cell Biology

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Rules of engagement for condensins and cohesins guide mitotic chromosome formation

Samejima,

Gibcus,

Abraham

et al. 2024

Preprint

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During mitosis, interphase chromatin is rapidly converted into rod-shaped mitotic chromosomes. Using Hi-C, imaging, proteomics and polymer modeling, we determine how the activity and interplay between loop-extruding SMC motors accomplishes this dramatic transition. Our work reveals rules of engagement for SMC complexes that are critical for allowing cells to refold interphase chromatin into mitotic chromosomes. We find that condensin disassembles interphase chromatin loop organization by evicting or displacing extrusive cohesin. In contrast, condensin bypasses cohesive cohesins, thereby maintaining sister chromatid cohesion while separating the sisters. Studies of mitotic chromosomes formed by cohesin, condensin II and condensin I alone or in combination allow us to develop new models of mitotic chromosome conformation. In these models, loops are consecutive and not overlapping, implying that condensins do not freely pass one another but stall upon encountering each other. The dynamics of Hi-C interactions and chromosome morphology reveal that during prophase loops are extruded in vivo at ~1-3 kb/sec by condensins as they form a disordered discontinuous helical scaffold within individual chromatids.

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RecN and RecA orchestrate an ordered DNA supercompaction response following ciprofloxacin exposure inEscherichia coli

Vikedal,

Ræder,

Riisnæs

et al. 2024

Preprint

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Fluoroquinolones induce double-strand breaks in bacterial DNA, triggering the SOS response, a major DNA damage response that ensures the expression of repair proteins but also promotes the emergence and spread of antibiotic resistance. Fluoroquinolone resistance, particularly inEscherichia coli, is a growing global health concern. Understanding bacterial responses to these antibiotics is critical for developing preventive strategies and novel treatments to combat resistance development. This study investigates DNA morphology inE. colifollowing exposure to ciprofloxacin, a fluoroquinolone antibiotic. We show that ciprofloxacin induces a stepwise DNA reorganization, culminating in a highly dense nucleoid structure at midcell — a process we term DNA supercompaction. Live cell imaging revealed that RecN, a structural maintenance of chromosomes (SMC)-like protein, is required for DNA supercompaction, and that RecN’s dynamics and activity in this response depend on RecA. Additionally, RecN and RecA frequently colocalized at nucleoid-associated positions. We suggest that RecN and RecA play active roles in DNA supercompaction following severe DNA damage, that their interplay is part of a prompt universal survival response to DNA double-strand breaks inE. coli,and that the extent of the compaction response depends on the number of double-strand breaks. GRAPHICAL ABSTRACT

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DNA packaging by molecular motors: from bacteriophage to human chromosomes

Cited by 3 publications

References 188 publications

Near millimolar concentration of nucleosomes in mitotic chromosomes from late prometaphase into anaphase

Near millimolar concentration of nucleosomes in mitotic chromosomes from late prometaphase into anaphase

Rules of engagement for condensins and cohesins guide mitotic chromosome formation

RecN and RecA orchestrate an ordered DNA supercompaction response following ciprofloxacin exposure inEscherichia coli

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