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Review
. 2015 Nov 20;5(4):3204-59.
doi: 10.3390/biom5043204.

DNA Damage Signalling and Repair Inhibitors: The Long-Sought-After Achilles' Heel of Cancer

Denis Velic  1   2   3 , Anthony M Couturier  4   5 , Maria Tedim Ferreira  6   7 , Amélie Rodrigue  8   9 , Guy G Poirier  10   11 , Fabrice Fleury  12 , Jean-Yves Masson  13   14   15
Affiliations
Review

DNA Damage Signalling and Repair Inhibitors: The Long-Sought-After Achilles' Heel of Cancer

Denis Velic et al. Biomolecules. .

Abstract

For decades, radiotherapy and chemotherapy were the two only approaches exploiting DNA repair processes to fight against cancer. Nowadays, cancer therapeutics can be a major challenge when it comes to seeking personalized targeted medicine that is both effective and selective to the malignancy. Over the last decade, the discovery of new targeted therapies against DNA damage signalling and repair has offered the possibility of therapeutic improvements in oncology. In this review, we summarize the current knowledge of DNA damage signalling and repair inhibitors, their molecular and cellular effects, and future therapeutic use.

Keywords: ATM; ATR; CHK1; CHK2; DNA repair; MRE11; PARP; RAD51; inhibitors.

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Figures

Figure 1
Figure 1
The DNA damage response pathways and its inhibitors.
Figure 2
Figure 2
Schematic representation of DNA repair by homologous recombination. During Homologous Recombination (HR), the double-strand break is recognized by the MRE11-RAD50-NBS1 (MRN) (MRE11-RAD50-NBS1) complex, which resects DNA (with EXO1, CtIP and BLM) to create a 3'-overhang DNA that will be protected by RPA. The BRCA1-PALB2-BRCA2 complex then mediates the replacement of RPA by RAD51. RAD51 nucleoprotein filament, invades the complementary DNA template (a step called strand invasion), leading to the formation of the Displacement-loop (D-loop) structure. Following branch migration and resolution, faithful DNA repair occurs.
Figure 3
Figure 3
Schematic representation of DNA repair by non-homologous end-joining (NHEJ): classical NHEJ (C-NHEJ) or alternative NHEJ (alt-NHEJ).
Figure 4
Figure 4
The synthetic lethality pathway model based on a deficiency in Alt-NHEJ and the double-strand break repair pathway.
See this image and copyright information in PMC

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