TY - JOUR
T1 - DNA damage and autophagy
AU - Rodriguez-Rocha, Humberto
AU - Garcia-Garcia, Aracely
AU - Panayiotidis, Mihalis I.
AU - Franco, Rodrigo
N1 - Funding Information:
This work was supported by the National Institutes of Health Grant P20RR17675 , Centers of Biomedical Research Excellence (COBRE) and the Layman Award from the Office of Research of the University of Nebraska-Lincoln (R. Franco).
PY - 2011/6/3
Y1 - 2011/6/3
N2 - Both exogenous and endogenous agents are a threat to DNA integrity. Exogenous environmental agents such as ultraviolet (UV) and ionizing radiation, genotoxic chemicals and endogenous byproducts of metabolism including reactive oxygen species can cause alterations in DNA structure (DNA damage). Unrepaired DNA damage has been linked to a variety of human disorders including cancer and neurodegenerative disease. Thus, efficient mechanisms to detect DNA lesions, signal their presence and promote their repair have been evolved in cells. If DNA is effectively repaired, DNA damage response is inactivated and normal cell functioning resumes. In contrast, when DNA lesions cannot be removed, chronic DNA damage triggers specific cell responses such as cell death and senescence. Recently, DNA damage has been shown to induce autophagy, a cellular catabolic process that maintains a balance between synthesis, degradation, and recycling of cellular components. But the exact mechanisms by which DNA damage triggers autophagy are unclear. More importantly, the role of autophagy in the DNA damage response and cellular fate is unknown. In this review we analyze evidence that supports a role for autophagy as an integral part of the DNA damage response.
AB - Both exogenous and endogenous agents are a threat to DNA integrity. Exogenous environmental agents such as ultraviolet (UV) and ionizing radiation, genotoxic chemicals and endogenous byproducts of metabolism including reactive oxygen species can cause alterations in DNA structure (DNA damage). Unrepaired DNA damage has been linked to a variety of human disorders including cancer and neurodegenerative disease. Thus, efficient mechanisms to detect DNA lesions, signal their presence and promote their repair have been evolved in cells. If DNA is effectively repaired, DNA damage response is inactivated and normal cell functioning resumes. In contrast, when DNA lesions cannot be removed, chronic DNA damage triggers specific cell responses such as cell death and senescence. Recently, DNA damage has been shown to induce autophagy, a cellular catabolic process that maintains a balance between synthesis, degradation, and recycling of cellular components. But the exact mechanisms by which DNA damage triggers autophagy are unclear. More importantly, the role of autophagy in the DNA damage response and cellular fate is unknown. In this review we analyze evidence that supports a role for autophagy as an integral part of the DNA damage response.
KW - ATM
KW - Autophagic cell death
KW - Cancer
KW - Genotoxic stress
KW - P53
UR - http://www.scopus.com/inward/record.url?scp=79956220703&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79956220703&partnerID=8YFLogxK
U2 - 10.1016/j.mrfmmm.2011.03.007
DO - 10.1016/j.mrfmmm.2011.03.007
M3 - Short survey
C2 - 21419786
AN - SCOPUS:79956220703
SN - 0027-5107
VL - 711
SP - 158
EP - 166
JO - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
JF - Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
IS - 1-2
ER -