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Updated: Jul 11, 2026

Using Next Generation Sequencing to Identify Mutations Associated with Repair of a CAS9-induced Double Strand Break Near the CD4 Promoter
Published on: March 31, 2022
DNA strand break repair and human genetic disease
Peter J McKinnon1, Keith W Caldecott
1Department of Genetics and Tumor Cell Biology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Abstract:
Each day tens of thousands of DNA single-strand breaks (SSBs) arise in every cell from the attack of deoxyribose and DNA bases by reactive oxygen species and other electrophilic molecules. DNA double-strand breaks (DSBs) also arise, albeit at a much lower frequency, from similar attacks and from the encounter of unrepaired SSBs and possibly other DNA structures by DNA replication forks. DSBs are also created during normal development of the immune system. Defects in the cellular response to DNA strand breaks underpin many human diseases, including disorders associated with cancer predisposition, immune dysfunction, radiosensitivity, and neurodegeneration. Here we provide an overview of the genetic diseases associated with defects in the repair/response to DNA strand breaks.
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Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
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