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Curr Opin Genet Dev. 2014 Apr;25:93-100. doi: 10.1016/j.gde.2013.11.022. Epub 2014 Mar 2.

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

Author information

1
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
2
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA. Electronic address: gilbert@bio.fsu.edu.

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.

PMID:
24598232
PMCID:
PMC4140690
DOI:
10.1016/j.gde.2013.11.022
[Indexed for MEDLINE]
Free PMC Article

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