DNA choreography: correlating mobility and organization of DNA across different resolutions from loops to chromosomes.

The dynamics of DNA in the cell nucleus plays a role in cellular processes and fates but the interplay of DNA mobility with the hierarchical levels of DNA organization is still underexplored. Here, we made use of DNA replication to directly label genomic DNA in an unbiased genome-wide manner. This w...

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Publicado en:Histochemistry & Cell Biology Vol. 162; no. 1/2; pp. 109 - 132
Autores principales: Pabba, Maruthi K., Meyer, Janis, Celikay, Kerem, Schermelleh, Lothar, Rohr, Karl, Cardoso, M. Cristina
Formato: Journal Article
Publicado: Springer Nature Jul2024
Acceso en línea:Ver este registro en EBSCOhost
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        atl: DNA choreography: correlating mobility and organization of DNA across different resolutions from loops to chromosomes.
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          Pabba, Maruthi K.
          Meyer, Janis
          Celikay, Kerem
          Schermelleh, Lothar
          Rohr, Karl
          Cardoso, M. Cristina
        affil: https://ror.org/05n911h24 Department of Biology, Technical University of Darmstadt, Darmstadt, Germany
      sug:
      ab: The dynamics of DNA in the cell nucleus plays a role in cellular processes and fates but the interplay of DNA mobility with the hierarchical levels of DNA organization is still underexplored. Here, we made use of DNA replication to directly label genomic DNA in an unbiased genome-wide manner. This was followed by live-cell time-lapse microscopy of the labeled DNA combining imaging at different resolutions levels simultaneously and allowing one to trace DNA motion across organization levels within the same cells. Quantification of the labeled DNA segments at different microscopic resolution levels revealed sizes comparable to the ones reported for DNA loops using 3D super-resolution microscopy, topologically associated domains (TAD) using 3D widefield microscopy, and also entire chromosomes. By employing advanced chromatin tracking and image registration, we discovered that DNA exhibited higher mobility at the individual loop level compared to the TAD level and even less at the chromosome level. Additionally, our findings indicate that chromatin movement, regardless of the resolution, slowed down during the S phase of the cell cycle compared to the G1/G2 phases. Furthermore, we found that a fraction of DNA loops and TADs exhibited directed movement with the majority depicting constrained movement. Our data also indicated spatial mobility differences with DNA loops and TADs at the nuclear periphery and the nuclear interior exhibiting lower velocity and radius of gyration than the intermediate locations. On the basis of these insights, we propose that there is a link between DNA mobility and its organizational structure including spatial distribution, which impacts cellular processes.
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    language: English
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