Unwinding the mutational signatures of a DNA topoisomerase enzyme

Abbasi, Ammal; Alexandrov, Ludmil B.

doi:10.1038/d41586-022-00301-5

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09 February 2022

Unwinding the mutational signatures of a DNA topoisomerase enzyme

Certain patterns of mutations occur frequently in cancer. The culprit behind one mutational signature is now shown to be a cellular enzyme with the mundane role of relieving stress in supercoiled DNA.

Ammal Abbasi⁰ &
Ludmil B. Alexandrov¹

Ammal Abbasi
1. Ammal Abbasi is in the Departments of Cellular and Molecular Medicine and of Bioengineering, University of California San Diego, La Jolla, California 92093, USA, and is at the Moores Cancer Center, La Jolla.
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Ludmil B. Alexandrov
1. Ludmil B. Alexandrov is in the Departments of Cellular and Molecular Medicine and of Bioengineering, University of California San Diego, La Jolla, California 92093, USA, and is at the Moores Cancer Center, La Jolla.
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Cancers are fuelled by changes in DNA, known as driver mutations, that tip cells towards uncontrolled multiplication. The mutations vary from tumour to tumour and from person to person, but some common patterns are emerging from analyses of thousands of genomes from cancerous and normal human tissues¹. These analyses are providing reference sets of mutational ‘signatures’ that can be used to unpick the molecular processes underlying the mutations². Much progress has been made in understanding the events that underpin signatures involving the mutation of single DNA ‘letters’, or bases. But less is known about the causes of mutational footprints characterized by small insertions and deletions (indels) of DNA. Writing in Nature, Reijns et al.³ describe their comprehensive computational and experimental investigation of the foundations of one such signature.

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Nature 602, 580-581 (2022)

doi: https://doi.org/10.1038/d41586-022-00301-5

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