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

• Main Authors: Terrence Hanscom, Mitch McVey
• Format: Article
• Language: English
• Published: MDPI AG 2020-07-01
• Series: Cells
• Subjects: alt-EJ; polymerase theta; microhomology-mediated end joining; chromosome rearrangements; resection
• Online Access: https://www.mdpi.com/2073-4409/9/7/1657

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.