PDBsum entry 2lvm

Cell cycle

PDB id: 2lvm

Contents

Protein chains

123 a.a.

14 a.a.

PDB id:

2lvm

Name:

Cell cycle

Title:

Solution structure of human 53bp1 tandem tudor domains in complex with a histone h4k20me2 peptide

Structure:

Tumor suppressor p53-binding protein 1. Chain: a. Fragment: unp residues 1484-1603. Synonym: 53bp1, p53-binding protein 1, p53bp1. Engineered: yes. Histone h4. Chain: b. Fragment: unp residues 15-28. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tp53bp1. Expressed in: escherichia coli. Expression_system_taxid: 562.

NMR struc:

20 models

Authors:

G.Cui,M.Botuyan,G.Mer

Key ref:

J.Tang et al. (2013). Acetylation limits 53BP1 association with damaged chromatin to promote homologous recombination. Nat Struct Biol, 20, 317-325. PubMed id: 23377543 DOI: 10.1038/nsmb.2499

Date:

07-Jul-12 Release date: 12-Dec-12

Protein chain

Q12888  (TP53B_HUMAN) -  TP53-binding protein 1 from Homo sapiens

Seq: 1972 a.a.

Struc: 123 a.a.*

Protein chain

P62805  (H4_HUMAN) -  Histone H4 from Homo sapiens

Seq: 103 a.a.

Struc: 14 a.a.*

* PDB and UniProt seqs differ at 4 residue positions (black crosses)

DOI no: 10.1038/nsmb.2499

Nat Struct Biol 20:317-325 (2013)

PubMed id: 23377543

Acetylation limits 53BP1 association with damaged chromatin to promote homologous recombination.

J.Tang, N.W.Cho, G.Cui, E.M.Manion, N.M.Shanbhag, M.V.Botuyan, G.Mer, R.A.Greenberg.

ABSTRACT

The pathogenic sequelae of BRCA1 mutation in human and mouse cells are mitigated by concomitant deletion of 53BP1, which binds histone H4 dimethylated at Lys20 (H4K20me2) to promote nonhomologous end joining, suggesting that a balance between BRCA1 and 53BP1 regulates DNA double strand-break (DSB) repair mechanism choice. Here we document that acetylation is a key determinant of this balance. TIP60 acetyltransferase deficiency reduced BRCA1 at DSB chromatin with commensurate increases in 53BP1, whereas HDAC inhibition yielded the opposite effect. TIP60-dependent H4 acetylation diminished 53BP1 binding to H4K20me2 in part through disruption of a salt bridge between H4K16 and Glu1551 in the 53BP1 Tudor domain. Moreover, TIP60 deficiency impaired homologous recombination and conferred sensitivity to PARP inhibition in a 53BP1-dependent manner. These findings demonstrate that acetylation in cis to H4K20me2 regulates relative BRCA1 and 53BP1 DSB chromatin occupancy to direct DNA repair mechanism.