Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
Department of Biological Science, Florida State University, Tallahassee, FL 32306, USA.
Curr Opin Genet Dev. 2014 Apr;25:93-100. doi: 10.1016/j.gde.2013.11.022. Epub 2014 Mar 2.
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.
最近大量的报告将复制时间 (RT) 与进化和癌症过程中的突变率联系起来。具体来说，点突变和拷贝数损失与晚期复制相关，而拷贝数增加和其他重排则与早期复制相关。在某些情况下，已经提出了合理的机制。点突变率可能反映了修复机制的时间变化。转录诱导的双链断裂预计会发生在转录活跃的早期复制染色质中。融合伙伴通常彼此靠近，并且接近的染色质在相似的时间复制。然而，拷贝数增加和减少的时间富集仍然是一个谜。此外，许多结论受到缺乏匹配的 RT 和序列数据集、RT 中发育变化的过滤以及使用体细胞系对生殖系进化进行推断的影响。
