Intrinsic coupling of lagging-strand synthesis to chromatin assembly

摘要

DNA滞后链的复制涉及被连接在一起的离散的Okazaki片段的生成。核小体组装是与复制耦合在一起的，但这会怎样影响Okazaki片段的处理却不清楚。现在，Durlcan Smlth和lestyrWhitehouse发现，出乎意料的是，Okazaki片段的连接出现在包裹一个核小体的DNA的中点上，而不是出现在核小体之、司的区域。另外染色体组合体中所发生的改变或滞后链的聚合会影响Okazaki片段的大小，说明染色质的组合是OKazaki片段合成过程中断的个信号。%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 Sacckaromyces 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.