Cell
Volume 168, Issue 4, 9 February 2017, Pages 644-656
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Review
Endogenous DNA Damage as a Source of Genomic Instability in Cancer

https://doi.org/10.1016/j.cell.2017.01.002 Get rights and content
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Genome instability, defined as higher than normal rates of mutation, is a double-edged sword. As a source of genetic diversity and natural selection, mutations are beneficial for evolution. On the other hand, genomic instability can have catastrophic consequences for age-related diseases such as cancer. Mutations arise either from inactivation of DNA repair pathways or in a repair-competent background due to genotoxic stress from celluar processes such as transcription and replication that overwhelm high-fidelity DNA repair. Here, we review recent studies that shed light on endogenous sources of mutation and epigenomic features that promote genomic instability during cancer evolution.

Keywords

Genome instability
cancer
DNA damage
DNA repair
DNA replication
transcription
mutagenesis

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