%0 Journal Article
%T Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1.
%A Bacic L
%A Gaullier G
%A Mohapatra J
%A Mao G
%A Brackmann K
%A Panfilov M
%A Liszczak G
%A Sabantsev A
%A Deindl S
%J Nat Commun
%V 15
%N 1
%D 2024 Feb 2
%M 38307862
%F 17.694
%R 10.1038/s41467-024-45237-8
%X 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.