DONSON and FANCM associate with different replisomes distinguished by replication timing and chromatin domain

Jing Zhang, Marina A Bellani, Ryan C James, Durga Pokharel, Yongqing Zhang, John J Reynolds, Gavin S McNee, Andrew P Jackson, Grant S Stewart, Michael M Seidman

Research output: Contribution to journalArticlepeer-review

Abstract

Duplication of mammalian genomes requires replisomes to overcome numerous impediments during passage through open (eu) and condensed (hetero) chromatin. Typically, studies of replication stress characterize mixed populations of challenged and unchallenged replication forks, averaged across S phase, and model a single species of "stressed" replisome. Here, in cells containing potent obstacles to replication, we find two different lesion proximal replisomes. One is bound by the DONSON protein and is more frequent in early S phase, in regions marked by euchromatin. The other interacts with the FANCM DNA translocase, is more prominent in late S phase, and favors heterochromatin. The two forms can also be detected in unstressed cells. ChIP-seq of DNA associated with DONSON or FANCM confirms the bias of the former towards regions that replicate early and the skew of the latter towards regions that replicate late.

Original languageEnglish
Pages (from-to)3951
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 7 Aug 2020

Keywords

  • Cell Cycle Proteins/metabolism
  • Chromatin Immunoprecipitation Sequencing
  • DNA Helicases/metabolism
  • DNA Replication Timing
  • Euchromatin/metabolism
  • HeLa Cells
  • Heterochromatin/metabolism
  • Humans
  • Nuclear Proteins/metabolism
  • S Phase

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