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

Author

Listed:
  • Jing Zhang

    (Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health)

  • Marina A. Bellani

    (Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health)

  • Ryan C. James

    (Cornell University)

  • Durga Pokharel

    (Horizon Discovery)

  • Yongqing Zhang

    (Gene Expression and Genomics Unit, National Institute on Aging, National Institutes of Health)

  • John J. Reynolds

    (Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham)

  • Gavin S. McNee

    (Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham)

  • Andrew P. Jackson

    (MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh)

  • Grant S. Stewart

    (Institute of Cancer and Genomic Sciences, College of Medical and Dental Sciences, University of Birmingham)

  • Michael M. Seidman

    (Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health)

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.

Suggested Citation

  • 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, 2020. "DONSON and FANCM associate with different replisomes distinguished by replication timing and chromatin domain," Nature Communications, Nature, vol. 11(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-17449-1
    DOI: 10.1038/s41467-020-17449-1
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