Saltar al contenido
Merck

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

Nature (2013-06-14)
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, Daniel Durocher
RESUMEN

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.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
ANTI-FLAG® M2 monoclonal antibody produced in mouse, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Sigma-Aldrich
L-Lisina, ≥98% (TLC)
Sigma-Aldrich
Anti-α-tubulina monoclonal antibody produced in mouse, clone DM1A, ascites fluid
Sigma-Aldrich
L-Lysine monohydrochloride, from non-animal source, meets EP, JP, USP testing specifications, suitable for cell culture, 98.5-101.0%
Sigma-Aldrich
L-Lisina, crystallized, ≥98.0% (NT)
Sigma-Aldrich
L-Lysine monohydrochloride, reagent grade, ≥98% (HPLC)
Sigma-Aldrich
L-Lysine acetate salt, ≥98% (HPLC)
Supelco
L-Lysine monohydrochloride, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
L-Lysine monohydrochloride, BioUltra, ≥99.5% (AT)
Supelco
L-Lysine Acetate, Pharmaceutical Secondary Standard; Certified Reference Material
Supelco
L-Lysine monohydrochloride, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland