4.6 Review

Regulation of Error-Prone DNA Double-Strand Break Repair and Its Impact on Genome Evolution

Journal

CELLS
Volume 9, Issue 7, Pages -

Publisher

MDPI
DOI: 10.3390/cells9071657

Keywords

alt-EJ; polymerase theta; microhomology-mediated end joining; chromosome rearrangements; resection

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Funding

  1. National Science Foundation [MCB1716039]
  2. National Institutes of Health [P01GM10547, R01GM125827]

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Double-strand breaks are one of the most deleterious DNA lesions. Their repair via error-prone mechanisms can promote mutagenesis, loss of genetic information, and deregulation of the genome. These detrimental outcomes are significant drivers of human diseases, including many cancers. Mutagenic double-strand break repair also facilitates heritable genetic changes that drive organismal adaptation and evolution. In this review, we discuss the mechanisms of various error-prone DNA double-strand break repair processes and the cellular conditions that regulate them, with a focus on alternative end joining. We provide examples that illustrate how mutagenic double-strand break repair drives genome diversity and evolution. Finally, we discuss how error-prone break repair can be crucial to the induction and progression of diseases such as cancer.

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