6JXD
Human nucleosome core particle with cohesive end DNA termini
Summary for 6JXD
| Entry DOI | 10.2210/pdb6jxd/pdb |
| Descriptor | Histone H3.1, MANGANESE (II) ION, Histone H4, ... (11 entities in total) |
| Functional Keywords | nucleosome, dna binding protein-dna complex, dna binding protein, dna binding protein/dna |
| Biological source | Homo sapiens (Human) More |
| Total number of polymer chains | 10 |
| Total formula weight | 179137.84 |
| Authors | DeFalco, L.,Davey, C.A. (deposition date: 2019-04-23, release date: 2020-01-15, Last modification date: 2023-11-22) |
| Primary citation | Sharma, D.,De Falco, L.,Padavattan, S.,Rao, C.,Geifman-Shochat, S.,Liu, C.F.,Davey, C.A. PARP1 exhibits enhanced association and catalytic efficiency with gamma H2A.X-nucleosome. Nat Commun, 10:5751-5751, 2019 Cited by PubMed Abstract: The poly(ADP-ribose) polymerase, PARP1, plays a key role in maintaining genomic integrity by detecting DNA damage and mediating repair. γH2A.X is the primary histone marker for DNA double-strand breaks and PARP1 localizes to H2A.X-enriched chromatin damage sites, but the basis for this association is not clear. We characterize the kinetics of PARP1 binding to a variety of nucleosomes harbouring DNA double-strand breaks, which reveal that PARP1 associates faster with (γ)H2A.X- versus H2A-nucleosomes, resulting in a higher affinity for the former, which is maximal for γH2A.X-nucleosome that is also the activator eliciting the greatest poly-ADP-ribosylation catalytic efficiency. The enhanced activities with γH2A.X-nucleosome coincide with increased accessibility of the DNA termini resulting from the H2A.X-Ser139 phosphorylation. Indeed, H2A- and (γ)H2A.X-nucleosomes have distinct stability characteristics, which are rationalized by mutational analysis and (γ)H2A.X-nucleosome core crystal structures. This suggests that the γH2A.X epigenetic marker directly facilitates DNA repair by stabilizing PARP1 association and promoting catalysis. PubMed: 31848352DOI: 10.1038/s41467-019-13641-0 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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