Connecting the Dots: From DNA Damage and Repair to Aging

  title={Connecting the Dots: From DNA Damage and Repair to Aging},
  author={Mei-Ren Pan and Kaiyi Li and Shiaw-Yih Lin and Wen-Chun Hung},
  journal={International Journal of Molecular Sciences},
  • M. Pan, Kaiyi Li, W. Hung
  • Published 1 May 2016
  • Biology
  • International Journal of Molecular Sciences
Mammalian cells evolve a delicate system, the DNA damage response (DDR) pathway, to monitor genomic integrity and to prevent the damage from both endogenous end exogenous insults. Emerging evidence suggests that aberrant DDR and deficient DNA repair are strongly associated with cancer and aging. Our understanding of the core program of DDR has made tremendous progress in the past two decades. However, the long list of the molecules involved in the DDR and DNA repair continues to grow and the… 

Figures and Tables from this paper

DNA Damage Response and Immune Defense
This review provides an overview, from cellular to molecular pathways, on how DDR and the immune system communicate and share the crucial commitment of maintaining the genomic fitness.
DCLK1 and DNA Damage Response
The novel insights into the role of DCLK1 in DNA damage response are discussed, which demonstrate the importance of the involvement of a specific sensory kinase in DDR signals after genotoxic injury.
DNA Damage Response and Immune Defense: Links and Mechanisms
Recent advances on the understanding of the role of DDR in activating immune signaling are described and evidence gained is highlighted into which molecular and cellular pathways of DDR activate immune signaling, how DNA damage drives chronic inflammation, and how chronic inflammation causes DNA damage and pathology in humans.
Complex DNA Damage: A Route to Radiation-Induced Genomic Instability and Carcinogenesis
The paradigm shift for the role of radiation-induced systemic effects is also incorporated in this picture of IR-effects and consequences of complex DNA damage induction and its erroneous repair.
Role of DNA polymerase β oxidized nucleotide insertion in DNA ligation failure
The importance of coordination between pol β and DNA ligase I during BER is discussed, and how this could be a fundamental mechanism underlying human diseases such as cancer and neurodegeneration.
DNA Damage Response Signals Transduce Stress From Rheumatoid Arthritis Risk Factors Into T Cell Dysfunction
  • L. Shao
  • Biology, Medicine
    Front. Immunol.
  • 2018
It is illustrated that risk factors for RA, such as viral infections, environmental events, and genetic risk loci are combat with DDR signals, and the impaired DDR response of RA-associated T cells, in turn, triggers disease-related phenotypes.
Signaling Pathways, Chemical and Biological Modulators of Nucleotide Excision Repair: The Faithful Shield against UV Genotoxicity
The major upstream signaling pathways and molecules that could modulate the NER's activity are summarized and discussed to provide potential treatments for genetic DNA repair-based diseases.
DNA Damage and Repair in Degenerative Diseases 2016
  • G. Sáez
  • Biology
    International journal of molecular sciences
  • 2017
Repairing the induced lesions to its molecular structure by different endogenous or exogenous origin is crucial for the maintenance of homeostasis and biological functions of living organisms.
Coordination of DNA Base Excision Repair by Protein-Protein Interactions
This review focuses on direct interactions of proteins participating in BER with each other and with noncanonical factors found recently to modulate the efficiency of BER.


Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications.
How the development of various complementary methodologies has provided valuable insights into the spatiotemporal dynamics of DDR protein assembly/disassembly at sites of DNA strand breaks in eukaryotic cells is outlined.
DNA damage, aging, and cancer.
  • J. Hoeijmakers
  • Biology, Medicine
    The New England journal of medicine
  • 2009
Evidence that cancer and diseases of aging are two sides of the DNAdamage problem is presented, followed by an account of the derailment of genome guardian mechanisms in cancer and of how this cancerspecific phenomenon can be exploited for treatment.
DNA repair mechanisms in dividing and non-dividing cells.
Changes in DNA repair during aging
The changes in efficiency of mismatch repair (MMR), base excision repair (BER), nucleotide excison repair (NER) and double-strand break (DSB) repair systems during aging, and potential changes in DSB repair pathway usage that occur with age are discussed.
DNA damage and autophagy.
The DNA damage response: putting checkpoints in perspective
The inability to repair DNA damage properly in mammals leads to various disorders and enhanced rates of tumour development, and this work has shown that direct activation of DNA repair networks is needed to correct this problem.