Activation of ATM depends on chromatin interactions occurring before induction of DNA damage. Export

@article{citeulike:3847363, abstract = {Efficient and correct responses to double-stranded breaks (DSB) in chromosomal DNA are crucial for maintaining genomic stability and preventing chromosomal alterations that lead to cancer. The generation of DSB is associated with structural changes in chromatin and the activation of the protein kinase ataxia-telangiectasia mutated (ATM), a key regulator of the signalling network of the cellular response to DSB. The interrelationship between DSB-induced changes in chromatin architecture and the activation of ATM is unclear. Here we show that the nucleosome-binding protein HMGN1 modulates the interaction of ATM with chromatin both before and after DSB formation, thereby optimizing its activation. Loss of HMGN1 or ablation of its ability to bind to chromatin reduces the levels of ionizing radiation (IR)-induced ATM autophosphorylation and the activation of several ATM targets. IR treatments lead to a global increase in the acetylation of Lys 14 of histone H3 (H3K14) in an HMGN1-dependent manner and treatment of cells with histone deacetylase inhibitors bypasses the HMGN1 requirement for efficient ATM activation. Thus, by regulating the levels of histone modifications, HMGN1 affects ATM activation. Our studies identify a new mediator of ATM activation and demonstrate a direct link between the steady-state intranuclear organization of ATM and the kinetics of its activation after DNA damage.}, author = {Kim, Y. C. and Gerlitz, G. and Furusawa, T. and Catez, F. and Nussenzweig, A. and Oh, K. S. and Kraemer, K. H. and Shiloh, Y. and Bustin, M.}, citeulike-article-id = {3847363}, citeulike-linkout-0 = {http://dx.doi.org/10.1038/ncb1817}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/19079244}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=19079244}, day = {14}, doi = {10.1038/ncb1817}, issn = {1476-4679}, journal = {Nature cell biology}, keywords = {acetylation, atm, dna-damage, dsb, h3k14}, month = {January}, number = {1}, pages = {92--96}, posted-at = {2009-01-26 22:37:57}, priority = {2}, publisher = {Nature Publishing Group}, title = {Activation of ATM depends on chromatin interactions occurring before induction of DNA damage.}, url = {http://dx.doi.org/10.1038/ncb1817}, volume = {11}, year = {2009} }

TY - JOUR ID - citeulike:3847363 L3 - citeulike-article-id:3847363 N2 - Efficient and correct responses to double-stranded breaks (DSB) in chromosomal DNA are crucial for maintaining genomic stability and preventing chromosomal alterations that lead to cancer. The generation of DSB is associated with structural changes in chromatin and the activation of the protein kinase ataxia-telangiectasia mutated (ATM), a key regulator of the signalling network of the cellular response to DSB. The interrelationship between DSB-induced changes in chromatin architecture and the activation of ATM is unclear. Here we show that the nucleosome-binding protein HMGN1 modulates the interaction of ATM with chromatin both before and after DSB formation, thereby optimizing its activation. Loss of HMGN1 or ablation of its ability to bind to chromatin reduces the levels of ionizing radiation (IR)-induced ATM autophosphorylation and the activation of several ATM targets. IR treatments lead to a global increase in the acetylation of Lys 14 of histone H3 (H3K14) in an HMGN1-dependent manner and treatment of cells with histone deacetylase inhibitors bypasses the HMGN1 requirement for efficient ATM activation. Thus, by regulating the levels of histone modifications, HMGN1 affects ATM activation. Our studies identify a new mediator of ATM activation and demonstrate a direct link between the steady-state intranuclear organization of ATM and the kinetics of its activation after DNA damage. IS - 1 JF - Nature cell biology SN - 1476-4679 EP - 96 TI - Activation of ATM depends on chromatin interactions occurring before induction of DNA damage. PB - Nature Publishing Group VL - 11 SP - 92 KW - acetylation KW - atm KW - dna-damage KW - dsb KW - h3k14 AU - Kim, YC AU - Gerlitz, G AU - Furusawa, T AU - Catez, F AU - Nussenzweig, A AU - Oh, KS AU - Kraemer, KH AU - Shiloh, Y AU - Bustin, M PY - 2009/01/14/ UR - http://dx.doi.org/10.1038/ncb1817 ER -