6K1K

Human nucleosome core particle with H2A.X S139E variant

Summary for 6K1K

• Entry DOI: 10.2210/pdb6k1k/pdb
• Descriptor: Histone H3.1, Histone H4, Histone H2AX, ... (10 entities in total)
• Functional Keywords: nucleosome, h2a.x, dna binding protein-dna complex, dna binding protein/dna
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 10
• Total formula weight: 205697.24

Authors

Sharma, D.,De Falco, L.,Davey, C.A. (deposition date: 2019-05-10, 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

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: 31848352
DOI: 10.1038/s41467-019-13641-0

Experimental method

X-RAY DIFFRACTION (2.2 Å)