2LVM: Solution structure of human 53BP1 tandem Tudor domains in complex with a histone H4K20me2 peptide

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.
PDB ID: 2LVMDownload
MMDB ID: 105670
PDB Deposition Date: 2012/7/7
Updated in MMDB: 2012/12
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2LVM: dimeric; determined by author
Molecular Components in 2LVM
Label Count Molecule
Proteins (2 molecules)
Tumor Suppressor P53-binding Protein 1(Gene symbol: TP53BP1)
Molecule annotation
Histone H4(Gene symbol: HIST1H4I)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB