TY - JOUR
T1 - Corrupting the DNA damage response
T2 - A critical role for Rad52 in tumor cell survival
AU - Lieberman, Rachel
AU - You, Ming
N1 - Funding Information:
We thank Johnathan D. Ebben, Jing Pan, and Yongik Lee for comments that greatly improved the manuscript. This research was supported by NIH grants U19CA148127, R01CA205633, R01CA208648, R01CA223804 and R01CA134682.
Publisher Copyright:
© Lieberman and You.
PY - 2017/7/1
Y1 - 2017/7/1
N2 - The DNA damage response enables cells to survive, maintain genome integrity, and to safeguard the transmission of high-fidelity genetic information. Upon sensing DNA damage, cells respond by activating this multifaceted DNA damage response leading to restoration of the cell, senescence, programmed cell death, or genomic instability if the cell survives without proper repair. However, unlike normal cells, cancer cells maintain a marked level of genomic instability. Because of this enhanced propensity to accumulate DNA damage, tumor cells rely on homologous recombination repair as a means of protection from the lethal effect of both spontaneous and therapy-induced double-strand breaks (DSBs) in DNA. Thus, modulation of DNA repair pathways have important consequences for genomic instability within tumor cell biology and viability maintenance under high genotoxic stress. Efforts are underway to manipulate specific components of the DNA damage response in order to selectively induce tumor cell death by augmenting genomic instability past a viable threshold. New evidence suggests that RAD52, a component of the homologous recombination pathway, is important for the maintenance of tumor genome integrity. This review highlights recent reports indicating that reducing homologous recombination through inhibition of RAD52 may represent an important focus for cancer therapy and the specific efforts that are already demonstrating potential.
AB - The DNA damage response enables cells to survive, maintain genome integrity, and to safeguard the transmission of high-fidelity genetic information. Upon sensing DNA damage, cells respond by activating this multifaceted DNA damage response leading to restoration of the cell, senescence, programmed cell death, or genomic instability if the cell survives without proper repair. However, unlike normal cells, cancer cells maintain a marked level of genomic instability. Because of this enhanced propensity to accumulate DNA damage, tumor cells rely on homologous recombination repair as a means of protection from the lethal effect of both spontaneous and therapy-induced double-strand breaks (DSBs) in DNA. Thus, modulation of DNA repair pathways have important consequences for genomic instability within tumor cell biology and viability maintenance under high genotoxic stress. Efforts are underway to manipulate specific components of the DNA damage response in order to selectively induce tumor cell death by augmenting genomic instability past a viable threshold. New evidence suggests that RAD52, a component of the homologous recombination pathway, is important for the maintenance of tumor genome integrity. This review highlights recent reports indicating that reducing homologous recombination through inhibition of RAD52 may represent an important focus for cancer therapy and the specific efforts that are already demonstrating potential.
KW - DNA damage response
KW - Pre-clinical model
KW - Rad52
KW - Squamous cell carcinoma of the lung
KW - Tumor growth
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U2 - 10.18632/aging.101263
DO - 10.18632/aging.101263
M3 - Review article
C2 - 28722656
AN - SCOPUS:85026647869
VL - 9
SP - 1647
EP - 1659
JO - Aging
JF - Aging
SN - 0394-9532
IS - 7
ER -