title: Endogenous DNA Damage as a Source of Genomic Instability in Cancer.
abstract: 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.
authors.affiliation: Laboratory of Genome Integrity, NIH, Bethesda, MD 20892, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Tubbs
authors.affiliation: Laboratory of Genome Integrity, NIH, Bethesda, MD 20892, USA. Electronic address: andre_nussenzweig@nih.gov.
authors.forename: André
authors.initials: A
authors.lastname: Nussenzweig
mesh_terms: D002843:Chromatin / Q000737:chemistry; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D042822:Genomic Instability; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000235:genetics*; D015533:Transcriptional Activation
chemical_list: D002843:Chromatin
keywords: DNA damage; DNA repair; DNA replication; Genome instability; cancer; mutagenesis; transcription