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-Structure paper
Title | Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1. |
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Journal, issue, pages | Nat Commun, Vol. 15, Issue 1, Page 1000, Year 2024 |
Publish date | Feb 2, 2024 |
Authors | Luka Bacic / Guillaume Gaullier / Jugal Mohapatra / Guanzhong Mao / Klaus Brackmann / Mikhail Panfilov / Glen Liszczak / Anton Sabantsev / Sebastian Deindl / |
PubMed 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 ...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. |
External links | Nat Commun / PubMed:38307862 / PubMed Central |
Methods | EM (single particle) |
Resolution | 3.0 Å |
Structure data | EMDB-15777, PDB-8b0a: |
Source |
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Keywords | DNA BINDING PROTEIN / ALC1 / CHD1L / nucleosome / PARylation / ADP-ribosylation / post-translational modification / chromatin |