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Regulation of Error-Prone DNA Double-Strand Break Repair and Its Impact on Genome Evolution
Terrence Hanscom1, Mitch McVey1
1Department. of Biology, Tufts University, Medford, MA 02155, USA.
Abstract:
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.
Insights
Error-prone DNA double-strand break repair mechanisms can cause mutations and genome instability, driving diseases like cancer and facilitating evolution. Understanding these processes is key to disease treatment and evolutionary insights.
Area of Science:
- Genetics
- Molecular Biology
- Genomics
Background:
- Double-strand breaks (DSBs) are highly toxic DNA lesions.
- Their repair can be error-prone, leading to mutations and genomic instability.
- These outcomes are implicated in cancer development and evolution.
Purpose of the Study:
- To review error-prone DNA double-strand break repair mechanisms.
- To explore cellular regulation of these pathways.
- To highlight the role of mutagenic DSB repair in genome diversity, evolution, and disease.
Main Methods:
- Literature review of DNA repair mechanisms.
- Focus on alternative end joining (AEJ).
- Analysis of examples linking mutagenic repair to genome diversity and disease.
Main Results:
- Error-prone repair pathways, including AEJ, contribute to mutagenesis.
- Mutagenic DSB repair drives genome diversity and evolutionary adaptation.
- Dysregulated DSB repair is crucial in cancer induction and progression.
Conclusions:
- Error-prone DSB repair is a double-edged sword, enabling evolution but also causing disease.
- Understanding these mechanisms offers therapeutic targets for cancer.
- Further research into DSB repair regulation is vital.
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