Evidence for sequential and increasing activation of replication origins along replication timing gradients in the human genome.

ABSTRACT: Genome-wide replication timing studies have suggested that mammalian chromosomes consist of megabase-scale domains of coordinated origin firing separated by large originless transition regions. Here, we report a quantitative genome-wide analysis of DNA replication kinetics in several human cell types that contradicts this view. DNA combing in HeLa cells sorted into four temporal compartments of S phase shows that replication origins are spaced at 40 kb intervals and fire as small clusters whose synchrony increases during S phase and that replication fork velocity (mean 0.7 kb/min, maximum 2.0 kb/min) remains constant and narrowly distributed through S phase. However, multi-scale analysis of a genome-wide replication timing profile shows a broad distribution of replication timing gradients

SUBMITTER: Guilbaud G 

PROVIDER: S-EPMC3248390 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature