@article{321842031e504ee1a481c4dba9a8dc18,
title = "TIRR regulates 53BP1 by masking its histone methyl-lysine binding function",
abstract = "P53-binding protein 1 (53BP1) is a multi-functional double-strand break repair protein that is essential for class switch recombination in B lymphocytes and for sensitizing BRCA1-deficient tumours to poly-ADP-ribose polymerase-1 (PARP) inhibitors. Central to all 53BP1 activities is its recruitment to double-strand breaks via the interaction of the tandem Tudor domain with dimethylated lysine 20 of histone H4 (H4K20me2). Here we identify an uncharacterized protein, Tudor interacting repair regulator (TIRR), that directly binds the tandem Tudor domain and masks its H4K20me2 binding motif. Upon DNA damage, the protein kinase ataxia-telangiectasia mutated (ATM) phosphorylates 53BP1 and recruits RAP1-interacting factor 1 (RIF1) to dissociate the 53BP1-TIRR complex. However, overexpression of TIRR impedes 53BP1 function by blocking its localization to double-strand breaks. Depletion of TIRR destabilizes 53BP1 in the nuclear-soluble fraction and alters the double-strand break-induced protein complex centring 53BP1. These findings identify TIRR as a new factor that influences double-strand break repair using a unique mechanism of masking the histone methyl-lysine binding function of 53BP1.",
author = "Pascal Dran{\'e} and Brault, {Marie Eve} and Gaofeng Cui and Khyati Meghani and Shweta Chaubey and Alexandre Detappe and Nishita Parnandi and Yizhou He and Zheng, {Xiao Feng} and Botuyan, {Maria Victoria} and Alkmini Kalousi and Yewdell, {William T.} and Christian M{\"u}nch and Harper, {J. Wade} and Jayanta Chaudhuri and Evi Soutoglou and Georges Mer and Dipanjan Chowdhury",
note = "Funding Information: D.C. is supported by R01 AI101897-01 (National Institute of Allergy and Infectious Diseases) and R01CA142698-07 (National Cancer Institute), a Leukemia and Lymphoma Society Scholar Grant, the Claudia Adams Barr Program for Innovative Cancer Research, a Department of Defense Ovarian Cancer Award, a Breast SPORE Pilot Award, and a Robert and Deborah First Fund Award. G.M. is supported by National Institutes of Health grants R01 CA132878 and R01 GM116829, and a Mayo Clinic Brain Cancer SPORE Program Pilot Award (P50 CA108961). J.W.H. is supported by AG011085. J.C. is supported by National Institutes of Health/National Institute of Allergy and Infectious Disease grants (1RO1AI072194 and 1RO1AI124186) and a National Cancer Institute Cancer Center Support grant (P30CA008748). W.T.Y. is supported by a training grant from the National Cancer Institute (4T32CA009149-40).",
year = "2017",
month = mar,
day = "9",
doi = "10.1038/nature21358",
language = "English (US)",
volume = "543",
pages = "211--216",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7644",
}