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Transcription — guarding the genome by sensing DNA damage

Nature Reviews Cancer volume 4, pages 727–737 (2004)Cite this article

Abstract

Cells induce the expression of DNA-repair enzymes, activate cell-cycle checkpoints and, under some circumstances, undergo apoptosis in response to DNA-damaging agents. The mechanisms by which these cellular responses are triggered are not well understood, but there is recent evidence that the transcription machinery might be used in DNA-damage surveillance and in triggering DNA-damage responses to suppress mutagenesis. Transcription might also act as a DNA-damage dosimeter where the severity of blockage determines whether or not to induce cell death. Could transcription therefore be a potential therapeutic target for anticancer strategies?

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Figure 1: Cellular consequences of blocked transcription.
Figure 2: Recovery of RNA synthesis.
Figure 3: Balance between DNA-damage responses, cancer and ageing.

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Acknowledgements

We would like to thank The National Institute of Health, The Swedish Cancer Foundation, Cancer Research UK and the American Institute for Cancer Research for financial support.

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Authors and Affiliations

  1. the Department of Radiation Oncology, Division of Radiation and Cancer Biology, University of Michigan Medical School and Department of Environmental Health Sciences, University of Michigan Comprehensive Cancer Center, School of Public Health, University of Michigan, Ann Arbor, 48109-0936, Michigan, USA

    Mats Ljungman

  2. the Department of Surgery and Molecular Oncology, University of Dundee, Dundee DD1 9SY, Scotland, UK, and the Institute of Molecular and Cell Biology, 61 Biopolis Drive, Proteos, 138673, Singapore

    David P. Lane

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  1. Mats Ljungman
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Correspondence to Mats Ljungman.

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DATABASES

Cancer.gov

breast cancer

lung cancer

Entrez Gene

BCL2

BCL-XL

CDKN1A

CSA

CSB

Csb

cyclin B1

DDB2

Ku86

lamin A/C

MDM2

MLH1

MSH2

NUP160

p53

TAP

UBF

VHL

Xpa

Xpc

XPC

FURTHER INFORMATION

Mats Ljungmans' lab

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Ljungman, M., Lane, D. Transcription — guarding the genome by sensing DNA damage. Nat Rev Cancer 4, 727–737 (2004). https://doi.org/10.1038/nrc1435

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