Results: 2

1.
Figure 1

Figure 1. Model for the DDR. From: The DNA-damage response in human biology and disease.

The presence of a lesion in the DNA, which can lead to replication stalling, is recognized by various sensor proteins. These sensors initiate signaling pathways that impact a wide variety of cellular processes. See text for details.

Stephen P. Jackson, et al. Nature. ;461(7267):1071-1078.
2.

Figure 2. Exploitation of the DDR pathways to enhance therapeutic responses. From: The DNA-damage response in human biology and disease.

a, Normal cells have two DDR pathways, A and B. If one pathway (B) is eliminated, genome instability results, which can foster the evolution of a cancer cell. Addition of a inhibitor targeting the second pathway (A) leads to cell death. Normal cells that still retain an active B pathway, however, survive. b, Treatment with a PARP inhibitor selectively kills HR/BRCA-deficient cells. PARP inhibition impairs the repair of SSBs, which are converted to DSBs in S-phase. Such DSBs are effectively repaired by HR in non-cancerous cells but not in BRCA-deficient cells.

Stephen P. Jackson, et al. Nature. ;461(7267):1071-1078.

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