Nucleus

Genome stability is an essential component for all forms of life, influencing cellular proliferation and inheritance of genetic information to the next generation. As our understanding of DNA organization within the eukaryotic nucleus has improved, so has the realization that the same mechanisms governing DNA structure and function profoundly impact genome stability by influencing both the formation and repair of DNA damage. While the impact of genome organization on DNA damage and repair has become increasingly clear, the molecular processes linking genome organization and genome stability are only beginning to be understood.

The organization of genetic material impacts the location and frequency of mutagenesis in all kingdoms of life, influencing where DNA damage arises from endogenous sources such as transcription and replication as well as exogenous sources such as ultraviolet radiation. DNA organization and nuclear substructure also has profound effect on DNA repair by limiting or delaying damage sensing, altering histone modification turnover, and regulating the accessibility of DNA to repair factors. Recent advances in microscopy, biophysics, and DNA sequencing technologies have revealed dynamic interactions of DNA with its environment before and during the DNA damage response and uncovered intriguing physical constraints of DNA repair proteins as well as long-range movements involved in protecting genome integrity. A deeper understanding of how nuclear architecture influences the emergence of new DNA damage as well as the spatial and temporal regulation of DNA repair processes will provide important insights into how cells accumulate mutations, potentially revealing the etiology of cell both type- and situation-specific mutational signatures.

This Article Collection aims to bring together research advancing our understanding the myriad roles nuclear structure influences the formation and repair of DNA damage. This Article Collection welcomes original research, short reports, and review manuscripts aimed at defining how nuclear structure impacts the formation and resolution of DNA damage. Methods manuscripts describing or summarizing novel techniques to interrogate the relationship between nuclear organization and DNA damage formation or repair processes are also encouraged. This Article Collection aims to bring together research that advances our understanding on how DNA architecture influences genome stability.

Disclosure Statement: Dr. Barlow declares no conflict of interest regarding this work.

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