1XNI

Tandem Tudor Domain of 53BP1

Summary for 1XNI

• Entry DOI: 10.2210/pdb1xni/pdb
• Descriptor: Tumor suppressor p53-binding protein 1 (1 entity in total)
• Functional Keywords: beta-barrel, bent beta-sheet, cell cycle
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus: Q12888
• Total number of polymer chains: 10
• Total formula weight: 134472.31

Authors

Huyen, Y.,Zgheib, O.,DiTullio Jr., R.A.,Gorgoulis, V.G.,Zacharatos, P.,Petty, T.J.,Sheston, E.A.,Mellert, H.S.,Stavridi, E.S.,Halazonetis, T.D. (deposition date: 2004-10-05, release date: 2004-11-30, Last modification date: 2024-02-14)

Primary citation

Huyen, Y.,Zgheib, O.,DiTullio Jr., R.A.,Gorgoulis, V.G.,Zacharatos, P.,Petty, T.J.,Sheston, E.A.,Mellert, H.S.,Stavridi, E.S.,Halazonetis, T.D.
Methylated lysine 79 of histone H3 targets 53BP1 to DNA double-strand breaks
Nature, 432:406-411, 2004

PubMed Abstract: The mechanisms by which eukaryotic cells sense DNA double-strand breaks (DSBs) in order to initiate checkpoint responses are poorly understood. 53BP1 is a conserved checkpoint protein with properties of a DNA DSB sensor. Here, we solved the structure of the domain of 53BP1 that recruits it to sites of DSBs. This domain consists of two tandem tudor folds with a deep pocket at their interface formed by residues conserved in the budding yeast Rad9 and fission yeast Rhp9/Crb2 orthologues. In vitro, the 53BP1 tandem tudor domain bound histone H3 methylated on Lys 79 using residues that form the walls of the pocket; these residues were also required for recruitment of 53BP1 to DSBs. Suppression of DOT1L, the enzyme that methylates Lys 79 of histone H3, also inhibited recruitment of 53BP1 to DSBs. Because methylation of histone H3 Lys 79 was unaltered in response to DNA damage, we propose that 53BP1 senses DSBs indirectly through changes in higher-order chromatin structure that expose the 53BP1 binding site.

PubMed: 15525939
DOI: 10.1038/nature03114

Experimental method

X-RAY DIFFRACTION (2.8 Å)