4.3 Review

Understanding DNA organization, damage, and repair with super-resolution fluorescence microscopy

Journal

Publisher

IOP Publishing Ltd
DOI: 10.1088/2050-6120/abf239

Keywords

DNA damage; chromatin; super resolution microscopy; DNA structure; genomic integrity

Funding

  1. Australian Research Council Discovery Early Career Research Award - Australian Government [DE200100584]
  2. Australian Research Council [DP170104477]
  3. National Institute of Health [1R35GM134947-01, 1P01CA247773-01/5491]
  4. American Cancer Society [RSG DMC-16-241-01-DMC]
  5. V foundation for Cancer Research [D2018-020]
  6. Australian Research Council [DE200100584] Funding Source: Australian Research Council

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Super-resolution microscopy techniques are well-suited for probing the nanoscale landscape of genomic function and dysfunction, offering high spatial resolution and single molecule localization advantages. These advances have provided unprecedented insights into DNA structure and function and enabled characterization of subpopulations within a single cell. Ongoing development and application of these interdisciplinary techniques will continue to expand the toolbox available for research into the nanoscale genomic landscape.
Super-resolution microscopy (SRM) comprises a suite of techniques well-suited to probing the nanoscale landscape of genomic function and dysfunction. Offering the specificity and sensitivity that has made conventional fluorescence microscopy a cornerstone technique of biological research, SRM allows for spatial resolutions as good as 10 nanometers. Moreover, single molecule localization microscopies (SMLMs) enable examination of individual molecular targets and nanofoci allowing for the characterization of subpopulations within a single cell. This review describes how key advances in both SRM techniques and sample preparation have enabled unprecedented insights into DNA structure and function, and highlights many of these new discoveries. Ongoing development and application of these novel, highly interdisciplinary SRM assays will continue to expand the toolbox available for research into the nanoscale genomic landscape.

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