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We show that the lack of BLM causes a decrease in the autophosphorylation of ATM in mice mammary glands, which have lost one or both copies of BLM. In isogenic human cells, the DNA damage response (DDR) pathway was dampened in the absence of BLM, which negatively affected the recruitment of DDR factors onto the chromatin, thereby indicating a direct role of BLM in augmenting DDR. Mechanistically, this was due to the BLM-dependent dissociation of inactive ATM dimers into active monomers. Fragmentation analysis of BLM followed by kinase assays revealed a 20-mer BLM peptide (91\u2013110 aa), sufficient to enhance ATM-dependent p53 phosphorylation. ATM-mediated phosphorylation of BLM at Thr99 within BLM (91\u2013110) peptide enhanced ATM kinase activity due to its interaction with NBS1 and causing ATM monomerization. Delivery of phosphomimetic T99E counterpart of BLM (91\u2013110 aa) peptide led to ATM activation followed by restoration of the DDR even in the absence of ionizing irradiation (both in cells and in BLM knockout mice), indicating its role as a DDR agonist, which can be potentially used to prevent the initiation of neoplastic transformation.<\/jats:p>","DOI":"10.1093\/nar\/gkaf106","type":"journal-article","created":{"date-parts":[[2025,2,25]],"date-time":"2025-02-25T11:03:27Z","timestamp":1740481407000},"source":"Crossref","is-referenced-by-count":4,"title":["Phosphorylated BLM peptide acts as an agonist for DNA damage response"],"prefix":"10.1093","volume":"53","author":[{"given":"Ritu","family":"Agrawal","sequence":"first","affiliation":[{"name":"Biotechnology Research and Innovation Council\u2014National Institute of Immunology (BRIC-NII) , Aruna Asaf Ali Marg, New Delhi 110067,","place":["India"]},{"name":"Biotechnology Research and Innovation Council\u2014National Institute of Biomedical Genomics (BRIC-NIBMG) , Kalyani , West Bengal 741251,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Himanshi","family":"Agarwal","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Innovation Council\u2014National Institute of Immunology (BRIC-NII) , Aruna Asaf Ali Marg, New Delhi 110067,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chetana","family":"Mukherjee","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Innovation Council\u2014National Institute of Immunology (BRIC-NII) , Aruna Asaf Ali Marg, New Delhi 110067,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baishali","family":"Chakraborty","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Innovation Council\u2014National Institute of Immunology (BRIC-NII) , Aruna Asaf Ali Marg, New Delhi 110067,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vandana","family":"Sharma","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Innovation Council\u2014National Institute of Immunology (BRIC-NII) , Aruna Asaf Ali Marg, New Delhi 110067,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Tripathi","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Innovation Council\u2014National Institute of Immunology (BRIC-NII) , Aruna Asaf Ali Marg, New Delhi 110067,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nitin","family":"Kumar","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Innovation Council\u2014National Institute of Immunology (BRIC-NII) , Aruna Asaf Ali Marg, New Delhi 110067,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Swati","family":"Priya","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Innovation Council\u2014National Institute of Immunology (BRIC-NII) , Aruna Asaf Ali Marg, New Delhi 110067,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Gupta","sequence":"additional","affiliation":[{"name":"Regional Centre for Biotechnology , Faridabad 121001, Haryana,","place":["India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gagan\u00a0Deep","family":"Jhingan","sequence":"additional","affiliation":[{"name":"Valerian Chem Pvt. 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