Repair Pathway Choices and Consequences at the Double-Strand Break

By Raphael Ceccaldi, B. Rondinelli, A. D’Andrea. Trends in Cell Biology, 2015

1,377 citations recorded by the source corpus.

DNA double-strand breaks (DSBs) are cytotoxic lesions that threaten genomic integrity. Failure to repair a DSB has deleterious consequences, including genomic instability and cell death. Indeed, misrepair of DSBs can lead to inappropriate end-joining events, which commonly underlie oncogenic transformation due to chromosomal translocations. Typically, cells employ two main mechanisms to repair DSBs: homologous recombination (HR) and classical nonhomologous end joining (C-NHEJ). In addition, alternative error-prone DSB repair pathways, namely alternative end joining (alt-EJ) and single-strand annealing (SSA), have been recently shown to operate in many different conditions and to contribute to genome rearrangements and oncogenic transformation. Here, we review the mechanisms regulating DSB repair pathway choice, together with the potential interconnections between HR and the annealing-dependent error-prone DSB repair pathways.

Subfields: Molecular Biology, Oncology

View Paper: https://www.semanticscholar.org/paper/57e89d5aa33490850489d04e924b0512750a8041

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In Molecular Biology

1. J. D. de Bono
2. Mark J. O'Connor
3. Yves Pommier
4. Ruixue Huang
5. Pingkun Zhou

In Oncology

1. J. D. de Bono
2. Mark J. O'Connor
3. Yves Pommier

Citations in the corpus

• Laying a trap to kill cancer cells: PARP inhibitors and their mechanisms of action (2016, background): “Although PARP trapping may be central to the mechanism of action of these inhibitors, it is also clear that PARP plays multiple roles in DNA repair, including the repair of the DSBs, and that inhibiting PARP during this process may also be an important component of cancer cell killing (15, 77).”
• DNA damage repair: historical perspectives, mechanistic pathways and clinical translation for targeted cancer therapy (2021, background): “However, in non-cycling cells, DSB end resection is significantly reduced, facilitating the cNHEJ repair pathway.(97) Post-translational modification was also found to regulate end resection.”