RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. Export

@article{citeulike:4035098, abstract = {DNA double-strand breaks (DSBs) not only interrupt the genetic information, but also disrupt the chromatin structure, and both impairments require repair mechanisms to ensure genome integrity. We showed previously that RNF8-mediated chromatin ubiquitylation protects genome integrity by promoting the accumulation of repair factors at DSBs. Here, we provide evidence that, while RNF8 is necessary to trigger the DSB-associated ubiquitylations, it is not sufficient to sustain conjugated ubiquitin in this compartment. We identified RNF168 as a novel chromatin-associated ubiquitin ligase with an ability to bind ubiquitin. We show that RNF168 interacts with ubiquitylated H2A, assembles at DSBs in an RNF8-dependent manner, and, by targeting H2A and H2AX, amplifies local concentration of lysine 63-linked ubiquitin conjugates to the threshold required for retention of 53BP1 and BRCA1. Thus, RNF168 defines a new pathway involving sequential ubiquitylations on damaged chromosomes and uncovers a functional cooperation between E3 ligases in genome maintenance.}, author = {Doil, Carsten and Mailand, Niels and Bekker-Jensen, Simon and Menard, Patrice and Larsen, Dorthe Helena H. and Pepperkok, Rainer and Ellenberg, Jan and Panier, Stephanie and Durocher, Daniel and Bartek, Jiri and Lukas, Jiri and Lukas, Claudia}, citeulike-article-id = {4035098}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.cell.2008.12.041}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S009286740900004X}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19203579}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19203579}, day = {6}, doi = {10.1016/j.cell.2008.12.041}, issn = {1097-4172}, journal = {Cell}, keywords = {chromosome, damage, dna, repair, riddle, ubiquitin}, month = {February}, number = {3}, pages = {435--446}, posted-at = {2009-02-11 13:10:49}, priority = {2}, title = {RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins.}, url = {http://dx.doi.org/10.1016/j.cell.2008.12.041}, volume = {136}, year = {2009} }

TY - JOUR ID - citeulike:4035098 L3 - citeulike-article-id:4035098 N2 - DNA double-strand breaks (DSBs) not only interrupt the genetic information, but also disrupt the chromatin structure, and both impairments require repair mechanisms to ensure genome integrity. We showed previously that RNF8-mediated chromatin ubiquitylation protects genome integrity by promoting the accumulation of repair factors at DSBs. Here, we provide evidence that, while RNF8 is necessary to trigger the DSB-associated ubiquitylations, it is not sufficient to sustain conjugated ubiquitin in this compartment. We identified RNF168 as a novel chromatin-associated ubiquitin ligase with an ability to bind ubiquitin. We show that RNF168 interacts with ubiquitylated H2A, assembles at DSBs in an RNF8-dependent manner, and, by targeting H2A and H2AX, amplifies local concentration of lysine 63-linked ubiquitin conjugates to the threshold required for retention of 53BP1 and BRCA1. Thus, RNF168 defines a new pathway involving sequential ubiquitylations on damaged chromosomes and uncovers a functional cooperation between E3 ligases in genome maintenance. IS - 3 JF - Cell SN - 1097-4172 EP - 446 TI - RNF168 binds and amplifies ubiquitin conjugates on damaged chromosomes to allow accumulation of repair proteins. VL - 136 SP - 435 KW - chromosome KW - damage KW - dna KW - repair KW - riddle KW - ubiquitin AU - Doil, Carsten AU - Mailand, Niels AU - Bekker-Jensen, Simon AU - Menard, Patrice AU - Larsen, Dorthe Helena AU - Pepperkok, Rainer AU - Ellenberg, Jan AU - Panier, Stephanie AU - Durocher, Daniel AU - Bartek, Jiri AU - Lukas, Jiri AU - Lukas, Claudia PY - 2009/02/06/ UR - http://dx.doi.org/10.1016/j.cell.2008.12.041 ER -