Nature. 2012 Mar 14;483(7390):434-8. doi: 10.1038/nature10895.
Intrinsic coupling of lagging-strand synthesis to chromatin assembly.
Smith DJ, Whitehouse I.
Source
Molecular Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York
Avenue, New York, New York 10065, USA.
Abstract
Fifty per cent of the genome is discontinuously replicated on the lagging
strand as Okazaki fragments. Eukaryotic Okazaki fragments remain poorly
characterized and, because nucleosomes are rapidly deposited on nascent DNA,
Okazaki fragment processing and nucleosome assembly potentially affect one
another. Here we show that ligation-competent Okazaki fragments in
Saccharomyces cerevisiae are sized according to the nucleosome repeat. Using
deep sequencing, we demonstrate that ligation junctions preferentially
occur near nucleosome midpoints rather than in internucleosomal linker
regions. Disrupting chromatin assembly or lagging-strand polymerase
processivity affects both the size and the distribution of Okazaki fragments
, suggesting a role for nascent chromatin, assembled immediately after the
passage of the replication fork, in the termination of Okazaki fragment
synthesis. Our studies represent the first high-resolution analysis--to our
knowledge--of eukaryotic Okazaki fragments in vivo, and reveal the
interconnection between lagging-strand synthesis and chromatin assembly.