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Trends Cell Biol. 2016 Jan;26(1):52-64. doi: 10.1016/j.tcb.2015.07.009. Epub 2015 Oct 1.

Repair Pathway Choices and Consequences at the Double-Strand Break.

Author information

1
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
2
Department of Radiation Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA. Electronic address: alan_dandrea@dfci.harvard.edu.

Abstract

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.

KEYWORDS:

DNA repair; Polθ; alternative end joining; homologous recombination; synthetic lethality

PMID:
26437586
PMCID:
PMC4862604
DOI:
10.1016/j.tcb.2015.07.009
[Indexed for MEDLINE]
Free PMC Article

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