8B0A
Cryo-EM structure of ALC1 bound to an asymmetric, site-specifically PARylated nucleosome
Summary for 8B0A
| Entry DOI | 10.2210/pdb8b0a/pdb |
| Related | 7otq |
| EMDB information | 13065 13070 15777 |
| Descriptor | Chromodomain-helicase-DNA-binding protein 1-like, Histone H3, Histone H4, ... (7 entities in total) |
| Functional Keywords | alc1, chd1l, nucleosome, parylation, adp-ribosylation, post-translational modification, chromatin, dna binding protein |
| Biological source | Homo sapiens (human) More |
| Total number of polymer chains | 11 |
| Total formula weight | 306814.43 |
| Authors | Bacic, L.,Gaullier, G.,Deindl, S. (deposition date: 2022-09-07, release date: 2023-09-20, Last modification date: 2024-04-03) |
| Primary citation | Bacic, L.,Gaullier, G.,Mohapatra, J.,Mao, G.,Brackmann, K.,Panfilov, M.,Liszczak, G.,Sabantsev, A.,Deindl, S. Asymmetric nucleosome PARylation at DNA breaks mediates directional nucleosome sliding by ALC1. Nat Commun, 15:1000-1000, 2024 Cited by 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 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. PubMed: 38307862DOI: 10.1038/s41467-024-45237-8 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3 Å) |
Structure validation
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