PDBsum entry 6jxd

DNA binding protein/DNA

PDB id: 6jxd

Contents

Protein chains

98 a.a.

80 a.a.

107 a.a.

97 a.a.

87 a.a.

DNA/RNA

Metals

_MN ×17

Waters ×52

PDB id:

6jxd

Name:

DNA binding protein/DNA

Title:

Human nucleosome core particle with cohesive end DNA termini

Structure:

Histone h3.1. Chain: a. Synonym: histone h3/a,histone h3/b,histone h3/c,histone h3/d,histone h3/f,histone h3/h,histone h3/i,histone h3/j,histone h3/k,histone h3/l. Engineered: yes. Histone h4. Chain: b. Engineered: yes.

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: hist1h3a, h3fa, hist1h3b, h3fl, hist1h3c, h3fc, hist1h3d, h3fb, hist1h3e, h3fd, hist1h3f, h3fi, hist1h3g, h3fh, hist1h3h, h3fk, hist1h3i, h3ff, hist1h3j, h3fj. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: hist1h4a, h4/a, h4fa, hist1h4b, h4/i, h4fi, hist1h4c, h4/g,

Resolution:

2.25Å R-factor: 0.240 R-free: 0.292

Authors:

L.Defalco,C.A.Davey

Key ref:

D.Sharma et al. (2019). PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome. Nat Commun, 10, 5751. PubMed id: 31848352 DOI: 10.1038/s41467-019-13641-0

Date:

23-Apr-19 Release date: 15-Jan-20

Protein chains

P68431  (H31_HUMAN) -  Histone H3.1 from Homo sapiens

Seq: 136 a.a.

Struc: 98 a.a.

Protein chain

P62805  (H4_HUMAN) -  Histone H4 from Homo sapiens

Seq: 103 a.a.

Struc: 80 a.a.

Protein chains

P04908  (H2A1B_HUMAN) -  Histone H2A type 1-B/E from Homo sapiens

Seq: 130 a.a.

Struc: 107 a.a.*

Protein chains

P06899  (H2B1J_HUMAN) -  Histone H2B type 1-J from Homo sapiens

Seq: 126 a.a.

Struc: 97 a.a.

Protein chain

P62805  (H4_HUMAN) -  Histone H4 from Homo sapiens

Seq: 103 a.a.

Struc: 87 a.a.

* PDB and UniProt seqs differ at 1 residue position (black cross)

DNA/RNA chains

C-A-T-A-T-A-T-C-C-C-G-G-T-G-C-C-G-A-G-G-C-C-G-C-T-C-A-A-T-T-G-G-T-C-G-T-A-G-A- 147 bases

C-A-T-A-T-A-T-G-C-C-G-G-T-C-T-C-A-C-A-C-G-T-G-C-C-T-G-G-A-G-A-C-T-A-G-T-A-A-G- 147 bases

DOI no: 10.1038/s41467-019-13641-0

Nat Commun 10:5751 (2019)

PubMed id: 31848352

PARP1 exhibits enhanced association and catalytic efficiency with γH2A.X-nucleosome.

D.Sharma, L.De Falco, S.Padavattan, C.Rao, S.Geifman-Shochat, C.F.Liu, C.A.Davey.

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.