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Complex correlations: replication timing and mutational landscapes during cancer and genome evolution

Authors
  • Sima, Jiao
  • Gilbert, David M1
  • 1 Department of Biological Science, Florida State University
Type
Published Article
Journal
Current Opinion in Genetics & Development
Publisher
Elsevier
Publication Date
Jan 01, 2014
Volume
25
Pages
93–100
Identifiers
DOI: 10.1016/j.gde.2013.11.022
Source
Elsevier
License
Unknown

Abstract

A recent flurry of reports correlates replication timing (RT) with mutation rates during both evolution and cancer. Specifically, point mutations and copy number losses correlate with late replication, while copy number gains and other rearrangements correlate with early replication. In some cases, plausible mechanisms have been proposed. Point mutation rates may reflect temporal variation in repair mechanisms. Transcription-induced double-strand breaks are expected to occur in transcriptionally active early replicating chromatin. Fusion partners are generally in close proximity, and chromatin in close proximity replicates at similar times. However, temporal enrichment of copy number gains and losses remains an enigma. Moreover, many conclusions are compromised by a lack of matched RT and sequence datasets, the filtering out of developmental variation in RT, and the use of somatic cell lines to make inferences about germline evolution.

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