TY - JOUR
T1 - Systemic DNA damage responses in aging and diseases
AU - Ribezzo, Flavia
AU - Shiloh, Yosef
AU - Schumacher, Björn
N1 - Publisher Copyright:
© 2016 Elsevier Ltd.
PY - 2016/6/1
Y1 - 2016/6/1
N2 - The genome is constantly attacked by a variety of genotoxic insults. The causal role for DNA damage in aging and cancer is exemplified by genetic defects in DNA repair that underlie a broad spectrum of acute and chronic human disorders that are characterized by developmental abnormalities, premature aging, and cancer predisposition. The disease symptoms are typically tissue-specific with uncertain genotype-phenotype correlation. The cellular DNA damage response (DDR) has been extensively investigated ever since yeast geneticists discovered DNA damage checkpoint mechanisms, several decades ago. In recent years, it has become apparent that not only cell-autonomous but also systemic DNA damage responses determine the outcome of genome instability in organisms. Understanding the mechanisms of non-cell-autonomous DNA damage responses will provide important new insights into the role of genome instability in human aging and a host of diseases including cancer and might better explain the complex phenotypes caused by genome instability.
AB - The genome is constantly attacked by a variety of genotoxic insults. The causal role for DNA damage in aging and cancer is exemplified by genetic defects in DNA repair that underlie a broad spectrum of acute and chronic human disorders that are characterized by developmental abnormalities, premature aging, and cancer predisposition. The disease symptoms are typically tissue-specific with uncertain genotype-phenotype correlation. The cellular DNA damage response (DDR) has been extensively investigated ever since yeast geneticists discovered DNA damage checkpoint mechanisms, several decades ago. In recent years, it has become apparent that not only cell-autonomous but also systemic DNA damage responses determine the outcome of genome instability in organisms. Understanding the mechanisms of non-cell-autonomous DNA damage responses will provide important new insights into the role of genome instability in human aging and a host of diseases including cancer and might better explain the complex phenotypes caused by genome instability.
KW - Aging
KW - Ataxia-telangiectasia mutated
KW - Cancer
KW - DNA damage response
KW - DNA repair
KW - Nucleotide excision repair
KW - Systemic DNA damage response
UR - http://www.scopus.com/inward/record.url?scp=84969218969&partnerID=8YFLogxK
U2 - 10.1016/j.semcancer.2015.12.005
DO - 10.1016/j.semcancer.2015.12.005
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C2 - 26773346
AN - SCOPUS:84969218969
SN - 1044-579X
VL - 37-38
SP - 26
EP - 35
JO - Seminars in Cancer Biology
JF - Seminars in Cancer Biology
ER -