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, 3 (1), e1030538
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Autophagy Is Critically Required for DNA Repair by Homologous Recombination

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Autophagy Is Critically Required for DNA Repair by Homologous Recombination

David A Gillespie et al. Mol Cell Oncol.

Abstract

Autophagy delivers damaged cytoplasmic constituents to lysosomes for degradation, thus preserving cellular integrity and protecting against disease. Remarkably, autophagy-deficient cells also exhibit aberrant DNA damage responses with therapeutic implications, such as suppression of checkpoint kinase-1 function, impaired DNA double-strand break repair by homologous recombination, and increased reliance on error-prone non-homologous end-joining for survival.

Keywords: Chk1; DNA repair; autophagy; homologous recombination.

Figures

Figure 1.
Figure 1.
Loss of autophagy impairs DNA repair by homologous recombination and uncovers a synthetic lethal strategy to kill autophagy-deficient cells. Cells with deletion of the essential autophagy gene Atg7 exhibit degradation and attenuated activation of checkpoint kinase 1 (Chk1) and diminished repair of DNA double-strand breaks by homologous recombination. Consequently, cells lacking autophagy become hyperdependent on non-homologous end joining for repair of DNA double-strand breaks. As a result, inhibition of non-homologous end joining prior to induction of DNA-damage causes persistence of genetic lesions and synthetic lethal killing of autophagy-deficient cells. DNA-PK, DNA-dependent protein kinase.

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