53BP1 is a reader of the DNA damage-induced H2A Lys15 ubiquitin mark
By Amélie Fradet-Turcotte, M. Canny, Cristina Escribano-Díaz, Alexandre Orthwein, C. Leung, Hao Huang, Marie-Claude Landry, Julianne Kitevski-LeBlanc, S. M. Noordermeer, F. Sicheri and 1 more. Nature, 2013
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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.
Subfields: Molecular Biology, Oncology
View Paper: https://www.semanticscholar.org/paper/452492869295212320b108a41f24b86a3e5afed8
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Citations in the corpus
- Phosphorylation-dependent assembly of DNA damage response systems and the central roles of TOPBP1 (2021, background): “4 μM, in vitro) [11] is a key step in the amplification and spreading of the γH2AX signal via recruitment of MRN and ATM, which in metazoan cells also facilitates recruitment of 53BP1 and the associated Shieldin complex to DNA double strand breaks, through ubiquitylation of histone H2A [12, 13].”