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Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1

Author

Listed:
  • Luka Bacic

    (Uppsala University)

  • Guillaume Gaullier

    (Uppsala University
    Uppsala University)

  • Jugal Mohapatra

    (The University of Texas Southwestern Medical Center)

  • Guanzhong Mao

    (Uppsala University)

  • Klaus Brackmann

    (Uppsala University)

  • Mikhail Panfilov

    (Uppsala University)

  • Glen Liszczak

    (The University of Texas Southwestern Medical Center)

  • Anton Sabantsev

    (Uppsala University)

  • Sebastian Deindl

    (Uppsala University)

Abstract

The chromatin remodeler ALC1 is activated by DNA damage-induced poly(ADP-ribose) deposited by PARP1/PARP2 and their co-factor HPF1. ALC1 has emerged as a cancer drug target, but how it is recruited to ADP-ribosylated nucleosomes to affect their positioning near DNA breaks is unknown. Here we find that PARP1/HPF1 preferentially initiates ADP-ribosylation on the histone H2B tail closest to the DNA break. To dissect the consequences of such asymmetry, we generate nucleosomes with a defined ADP-ribosylated H2B tail on one side only. The cryo-electron microscopy structure of ALC1 bound to such an asymmetric nucleosome indicates preferential engagement on one side. Using single-molecule FRET, we demonstrate that this asymmetric recruitment gives rise to directed sliding away from the DNA linker closest to the ADP-ribosylation site. Our data suggest a mechanism by which ALC1 slides nucleosomes away from a DNA break to render it more accessible to repair factors.

Suggested Citation

  • Luka Bacic & Guillaume Gaullier & Jugal Mohapatra & Guanzhong Mao & Klaus Brackmann & Mikhail Panfilov & Glen Liszczak & Anton Sabantsev & Sebastian Deindl, 2024. "Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45237-8
    DOI: 10.1038/s41467-024-45237-8
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    References listed on IDEAS

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