Structural Basis for the Methylation State-Specific Recognition of Histone H4-K20 by 53BP1 and Crb2 in DNA Repair

Maria Victoria Botuyan, Joseph Lee, Irene M. Ward, Ja Eun Kim, James R. Thompson, Junjie Chen, Georges Mer

Research output: Contribution to journalArticle

638 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1361-1373
Number of pages13
JournalCell
Volume127
Issue number7
DOIs
StatePublished - Dec 29 2006

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Methylation
DNA Repair
Histones
Repair
DNA
Double-Stranded DNA Breaks
Schizosaccharomyces
X ray crystallography
X Ray Crystallography
Yeast
Nuclear magnetic resonance spectroscopy
Lysine
Conservation
Magnetic Resonance Spectroscopy
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Structural Basis for the Methylation State-Specific Recognition of Histone H4-K20 by 53BP1 and Crb2 in DNA Repair. / Botuyan, Maria Victoria; Lee, Joseph; Ward, Irene M.; Kim, Ja Eun; Thompson, James R.; Chen, Junjie; Mer, Georges.

In: Cell, Vol. 127, No. 7, 29.12.2006, p. 1361-1373.

Research output: Contribution to journalArticle

Botuyan, Maria Victoria ; Lee, Joseph ; Ward, Irene M. ; Kim, Ja Eun ; Thompson, James R. ; Chen, Junjie ; Mer, Georges. / Structural Basis for the Methylation State-Specific Recognition of Histone H4-K20 by 53BP1 and Crb2 in DNA Repair. In: Cell. 2006 ; Vol. 127, No. 7. pp. 1361-1373.
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