How cancer cells hijack DNA double-strand break repair pathways to gain genomic instability

Jeggo, Penny A and Lobrich, Markus (2015) How cancer cells hijack DNA double-strand break repair pathways to gain genomic instability. Biochemical Journal, 471 (1). pp. 1-11. ISSN 0264-6021

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Abstract

DNA double-strand breaks (DSBs) are a significant threat to the viability of a normal cell, since they can result in loss of genetic material if mitosis or replication is attempted in their presence. Consequently, evolutionary pressure has resulted in multiple pathways and responses to enable DSBs to be repaired efficiently and faithfully. Cancer cells, which are under pressure to gain genomic instability, have a striking ability to avoid the elegant
mechanisms by which normal cells maintain genomic stability. Current models suggest that in normal cells DSB repair occurs in a hierarchical manner that promotes rapid and efficient rejoining first, with the utilisation of additional steps or pathways of diminished accuracy if
rejoining is unsuccessful or delayed. We evaluate the fidelity of DSB repair pathways and discuss how cancer cells promote the utilisation of less accurate processes. Homologous recombination serves to promote accuracy and stability during replication, providing a battlefield for cancer to gain instability. Non-homologous end-joining, a major DSB repair pathway in mammalian cells, usually operates with high fidelity and only switches to less
faithful modes if timely repair fails. The transition step is finely tuned and provides another point of attack during tumour progression. In addition to DSB repair, a DSB signalling response activates processes such as cell cycle checkpoint arrest, which enhance the possibility of accurate DSB repair. We will consider the ways by which cancers modify and accost these processes to gain genomic instability

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Penny Jeggo
Date Deposited: 18 Jan 2016 12:42
Last Modified: 13 Mar 2017 03:12
URI: http://sro.sussex.ac.uk/id/eprint/59276

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