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DNA double-strand breaks: their cellular and clinical impact?

journal contribution
posted on 2023-06-07, 14:44 authored by Penny Jeggo, M Löbrich
DNA, the central store of our genetic information, constantly incurs damage from agents generated within the cell as well as chemicals or radiation that arise externally. Of the many different classes of damage, a DNA double-strand break (DSB) is arguably the most significant since, if unrepaired it can result in cell death and if misrepaired, it can cause chromosomal translocations, an early step in the aetiology of carcinogenesis. Endogenously generated reactive oxygen species primarily induce base damage and single strand breaks and it is unlikely that DNA DSBs are directly induced to any significant extent. However, DSBs may arise indirectly from two closely located single-strand breaks or during the repair of other lesions. They also arise when replication forks collapse, which may occur following the attempted replication of single-strand breaks or base damage. Indeed, a DSB is very likely the ultimate lesion induced by a wide range of DNA-damaging agents. The enhanced levels of endogenous chromosome breakage or chromosome rearrangements that have been observed in cells that fail to repair DSBs efficiently attests to the fact that they represent a relatively frequently encountered endogenous lesion (Karanjawala et al., 1999). Despite the constant onslaught of endogenous oxidative damage as well as frequently encountered exogenous DNA damage, genomic changes are a rare event and cells can undergo multiple rounds of replication without witnessing chromosomal alterations. This attests to the remarkable efficiency and evolutionary importance of the pathways that function in response to DSB induction.

History

Publication status

  • Published

File Version

  • Submitted version

Journal

Oncogene

ISSN

0950-9232

Publisher

Nature Publishing Group

Issue

56

Volume

26

Page range

7717-7719

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2008-09-30

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