53BP1 is a reader of the DNA-damage-induced H2A Lys 15 ubiquitin mark

Amélie Fradet-Turcotte, Marella D. Canny, Cristina Escribano-Díaz, Alexandre Orthwein, Charles C. Y. Leung, Hao Huang, Marie-Claude Landry, Julianne Kitevski-LeBlanc, Sylvie M. Noordermeer, Frank Sicheri and Daniel Durocher ()
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Amélie Fradet-Turcotte: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue
Marella D. Canny: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue
Cristina Escribano-Díaz: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue
Alexandre Orthwein: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue
Charles C. Y. Leung: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue
Hao Huang: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue
Marie-Claude Landry: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue
Julianne Kitevski-LeBlanc: University of Toronto
Sylvie M. Noordermeer: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue
Frank Sicheri: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue
Daniel Durocher: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue

Nature, 2013, vol. 499, issue 7456, 50-54

Abstract: Abstract 53BP1 (also called TP53BP1) is a chromatin-associated factor that promotes immunoglobulin class switching and DNA double-strand-break (DSB) repair by non-homologous end joining. To accomplish its function in DNA repair, 53BP1 accumulates at DSB sites downstream of the RNF168 ubiquitin ligase. How ubiquitin recruits 53BP1 to break sites remains unknown as its relocalization involves recognition of histone H4 Lys 20 (H4K20) methylation by its Tudor domain. Here we elucidate how vertebrate 53BP1 is recruited to the chromatin that flanks DSB sites. We show that 53BP1 recognizes mononucleosomes containing dimethylated H4K20 (H4K20me2) and H2A ubiquitinated on Lys 15 (H2AK15ub), the latter being a product of RNF168 action on chromatin. 53BP1 binds to nucleosomes minimally as a dimer using its previously characterized methyl-lysine-binding Tudor domain and a carboxy-terminal extension, termed the ubiquitination-dependent recruitment (UDR) motif, which interacts with the epitope formed by H2AK15ub and its surrounding residues on the H2A tail. 53BP1 is therefore a bivalent histone modification reader that recognizes a histone ‘code’ produced by DSB signalling.

Date: 2013
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DOI: 10.1038/nature12318

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