Perturbations in the Replication Program Contribute to Genomic Instability in Cancer

Abstract

Cancer and genomic instability are highly impacted by the deoxyribonucleic acid (DNA) replication program. Inaccuracies in DNA replication lead to the increased acquisition of mutations and structural variations. These inaccuracies mainly stem from loss of DNA fidelity due to replication stress or due to aberrations in the temporal organization of the replication process. Here we review the mechanisms and impact of these major sources of error to the replication program.

Keywords: cancer; genomic instability; replication stress; replication timing.

Figure 1

Representative replication timing profiles. (a) An example of a replication timing map of mouse embryonic fibroblasts (MEF) [111] for a 2 Mb-sized region labeled by region type: TTR (timing transition region) or CTR (constant timing region); (b) The same replication timing map with annotation of the regions prone to various types of mutations.

Figure 1

Representative replication timing profiles. (a) An example of a replication timing map of mouse embryonic fibroblasts (MEF) [111] for a 2 Mb-sized region labeled by region type: TTR (timing transition region) or CTR (constant timing region); (b) The same replication timing map with annotation of the regions prone to various types of mutations.