DNA Damage Response

Kum Kum Khanna, The Queensland Institute of Medical Research, Brisbane, Australia
Randal S Tibbetts, The University of Wisconsin, Madison, Wisconsin, USA

Published online: January 2006

DOI: 10.1038/npg.els.0006107

The deoxyribonucleic acid (DNA) damage response pathway is a surveillance network whereby lesions are eliminated from DNA. DNA damage response detects aberrant DNA and chromosomal structures and coordinates it in some manner with each of the other DNA transactions, including regulation of the cell cycle, DNA repair, replication and under some circumstances the triggering of programmed cell death. Many aspects of DNA damage signaling are highly conserved throughout evolution.

Keywords: cell cycle arrest; DNA repair; ionizing radiation; damage detection; signal modifiers

Figure 1. Schematic representation of the DNA damage response pathway. In this model, DNA damage is recognized by a sensor, which transmits the signal to the ATM/ATR protein kinases. ATM/ATR-dependent signals are then transduced to the Chk1 and Chk2 protein kinases by a series of adaptors and signal modifiers. End points for the DNA damage response, including cell cycle arrest, DNA repair, gene transcription and apoptotic cell death, are shown.
Figure 2. Activation of DNA damage checkpoint pathways. ATM/ATR are activated in response to DNA damage by an unknown mechanism. Activated proteins signal the presence of DNA damage by phosphorylating targets involved in cell cycle arrest and DNA repair. ATM primarily regulates these phosphorylation events in response to IR (DSBs) and ATR controls it after exposure of cells to UV light and replication arrest (stalled forks).
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 Web Links
    ePath Ataxia telangiectasia and Rad3 related (ATR); Locus ID: 545. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=545
    ePath MRE11 meiotic recombination 11 homolog A (S. cerevisiae) (MRE11A); Locus ID: 4361. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4361
    ePath Nijmegen breakage syndrome 1 (nibrin) (NBS1); Locus ID: 4683. LocusLink: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=4683
    ePath Ataxia telangiectasia and Rad3 related (ATR); MIM number: 601215. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?601215
    ePath MRE11 meiotic recombination 11 homolog A (S. cerevisiae) (MRE11A); MIM number: 600814. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?600814
    ePath Nijmegen breakage syndrome 1 (nibrin) (NBS1); MIM number: 602667. OMIM: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?602667

Related Sub-Topics:

Mutational Mechanisms of Genetic Disease | Proteomic Studies of Genetic Disease | General Genetics and Disease | DNA Damage and Repair | Mechanisms of Cell Death, Senescence and Metabolism | Cell Signalling | Proteins: Structure, Function, Metabolism | Enzymes: Structure and Action Mechanism
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Article Title: DNA Damage Response
 
How to Cite close
Khanna, Kum Kum, and Tibbetts, Randal S(Jan 2006) DNA Damage Response. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0006107]