6k1k | pdb_00006k1k

Human nucleosome core particle with H2A.X S139E variant

spinqualitylabelsall models 6k1k, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6k1k is a 10 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.2Å Ligands: CL, K, MN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function H31_HUMAN Publication Abstract from PubMed The poly(ADP-ribose) polymerase, PARP1, plays a key role in maintaining genomic integrity by detecting DNA damage and mediating repair. gammaH2A.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 (gamma)H2A.X- versus H2A-nucleosomes, resulting in a higher affinity for the former, which is maximal for gammaH2A.X-nucleosome that is also the activator eliciting the greatest poly-ADP-ribosylation catalytic efficiency. The enhanced activities with gammaH2A.X-nucleosome coincide with increased accessibility of the DNA termini resulting from the H2A.X-Ser139 phosphorylation. Indeed, H2A- and (gamma)H2A.X-nucleosomes have distinct stability characteristics, which are rationalized by mutational analysis and (gamma)H2A.X-nucleosome core crystal structures. This suggests that the gammaH2A.X epigenetic marker directly facilitates DNA repair by stabilizing PARP1 association and promoting catalysis. PARP1 exhibits enhanced association and catalytic efficiency with gammaH2A.X-nucleosome.,Sharma D, De Falco L, Padavattan S, Rao C, Geifman-Shochat S, Liu CF, Davey CA Nat Commun. 2019 Dec 17;10(1):5751. doi: 10.1038/s41467-019-13641-0. PMID:31848352 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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