Repair of DNA double-strand breaks by mammalian alternative end-joining pathways

Alternative end-joining (a-EJ) pathways, which repair DNA double-strand breaks (DSBs), are initiated by end resection that generates 3′ single strands. This reaction is shared, at least in part, with homologous recombination but distinguishes a-EJ from the major nonhomologous end-joining pathway. Al...

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Bibliographic Details
Published in:The Journal of biological chemistry 2018-07, Vol.293 (27), p.10536-10546
Main Authors: Sallmyr, Annahita, Tomkinson, Alan E.
Format: Article
Language:English
Subjects:
alternative end-joining pathway
Animals
chromosomes
deletions
Disease - genetics
DNA Breaks, Double-Stranded
DNA damage
DNA End-Joining Repair
DNA endonuclease
DNA ligation
DNA polymerase
double-strand break
genomic instability
Homologous Recombination
Humans
microhomology
Signal Transduction
single-strand annealing
Thematic Minireviews
translocation
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Summary:Alternative end-joining (a-EJ) pathways, which repair DNA double-strand breaks (DSBs), are initiated by end resection that generates 3′ single strands. This reaction is shared, at least in part, with homologous recombination but distinguishes a-EJ from the major nonhomologous end-joining pathway. Although the a-EJ pathways make only a minor and poorly understood contribution to DSB repair in nonmalignant cells, there is growing interest in these pathways, as they generate genomic rearrangements that are hallmarks of cancer cells. Here, we review and discuss the current understanding of the mechanisms and regulation of a-EJ pathways, the role of a-EJ in human disease, and the potential utility of a-EJ as a therapeutic target in cancer.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.TM117.000375