2fhd

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Crystal structure of Crb2 tandem tudor domains

Structural highlights

2fhd is a 3 chain structure with sequence from Schizosaccharomyces pombe. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 2.4Å
Ligands:MSE, PO4
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

RHP9_SCHPO Essential for cell cycle arrest at the G1 and G2 stages following DNA damage by X-, and UV-irradiation, or inactivation of DNA ligase. Plays a role in the response to DNA damage.[1] [2] [3]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Histone lysine methylation has been linked to the recruitment of mammalian DNA repair factor 53BP1 and putative fission yeast homolog Crb2 to DNA double-strand breaks (DSBs), but how histone recognition is achieved has not been established. Here we demonstrate that this link occurs through direct binding of 53BP1 and Crb2 to histone H4. Using X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, we show that, despite low amino acid sequence conservation, both 53BP1 and Crb2 contain tandem tudor domains that interact with histone H4 specifically dimethylated at Lys20 (H4-K20me2). The structure of 53BP1/H4-K20me2 complex uncovers a unique five-residue 53BP1 binding cage, remarkably conserved in the structure of Crb2, that best accommodates a dimethyllysine but excludes a trimethyllysine, thus explaining the methylation state-specific recognition of H4-K20. This study reveals an evolutionarily conserved molecular mechanism of targeting DNA repair proteins to DSBs by direct recognition of H4-K20me2.

Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair.,Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G Cell. 2006 Dec 29;127(7):1361-73. PMID:17190600[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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References

  1. ↑ Willson J, Wilson S, Warr N, Watts FZ. Isolation and characterization of the Schizosaccharomyces pombe rhp9 gene: a gene required for the DNA damage checkpoint but not the replication checkpoint. Nucleic Acids Res. 1997 Jun 1;25(11):2138-46. PMID:9153313
  2. ↑ Saka Y, Esashi F, Matsusaka T, Mochida S, Yanagida M. Damage and replication checkpoint control in fission yeast is ensured by interactions of Crb2, a protein with BRCT motif, with Cut5 and Chk1. Genes Dev. 1997 Dec 15;11(24):3387-400. PMID:9407031
  3. ↑ Sanders SL, Portoso M, Mata J, Bahler J, Allshire RC, Kouzarides T. Methylation of histone H4 lysine 20 controls recruitment of Crb2 to sites of DNA damage. Cell. 2004 Nov 24;119(5):603-14. PMID:15550243 doi:http://dx.doi.org/10.1016/j.cell.2004.11.009
  4. ↑ Botuyan MV, Lee J, Ward IM, Kim JE, Thompson JR, Chen J, Mer G. Structural basis for the methylation state-specific recognition of histone H4-K20 by 53BP1 and Crb2 in DNA repair. Cell. 2006 Dec 29;127(7):1361-73. PMID:17190600 doi:10.1016/j.cell.2006.10.043

Contents


PDB ID 2fhd

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