Structural and Dynamical Signatures of Local DNA Damage in Live Cells
نویسندگان
چکیده
The dynamic organization of chromatin inside the cell nucleus plays a key role in gene regulation and genome replication, as well maintaining integrity. Although static folded state has been extensively studied, dynamical signatures processes such transcription or DNA repair remain an open question. Here, we investigate interphase dynamics human cells response to local damage, specifically, double-strand breaks (DSBs). Using simultaneous two-color spinning-disk confocal microscopy, monitor DSB compaction surrounding chromatin, visualized by fluorescently labeled 53BP1 histone H2B, respectively. Our study reveals surprising difference between mobility DSBs located nuclear interior versus periphery (less than 1 micron from envelope), with being almost twice mobile DSBs. Remarkably, find that sites possess robust structural signature form unique profile. Moreover, our data show motion is subdiffusive, ATP-dependent exhibits signatures, different those undamaged chromatin. findings reveal follows universal relationship defined solely physical parameters describing their environment, focus size (represented accumulation 53BP1), density, compaction. This suggests DSB-related are likely deterministic because observed (DSB mobility) can be explained features size, compaction). Such knowledge might help detecting damage live cells, aiding biophysical understanding integrity health disease. [Eaton, Zidovska, Biophys. J., 2020].
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2021
ISSN: ['0006-3495', '1542-0086']
DOI: https://doi.org/10.1016/j.bpj.2020.11.880