Endogenous DNA Damage as a Source of Genomic Instability in Cancer

• Published in: Cell Vol. 168; no. 4; pp. 644 - 656
• Main Authors: Tubbs, Anthony, Nussenzweig, André
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.02.2017
• Subjects: cancer; Chromatin - chemistry; DNA Damage; DNA Repair; DNA Replication; Genome instability; Genomic Instability; Humans; mutagenesis; Mutation; Neoplasms - genetics; transcription; Transcriptional Activation; DNA replication; transcription; DNA damage; Genome instability; cancer; DNA repair; mutagenesis
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2017.01.002

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. 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.