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Tat\u2010interactive protein 60\u2010kDa\/ataxia\u2013telangiectasia\u2010mutated (TIP60\/ATM) axis\u2010mediated DNA damage response (DDR) is vital for maintaining genomic integrity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Protein levels were detected by western blot, protein colocalisation was examined by immunofluorescence (IF) and protein interactions were measured by co\u2010immunoprecipitation, proximity ligation assay and GST pull\u2010down assays. Flow cytometry, comet assay and IF assays were used to explore the biological functions of sequence similarity 135 family member B (FAM135B) in DDR. Xenograft tumour, FAM135B transgenic mouse models and immunohistochemistry were utilised to confirm in vitro observations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified a novel DDR regulator FAM135B which could protect cancer cells from genotoxic stress in vitro and in vivo. The overexpression of FAM135B promoted the removal of \u03b3H2AX and 53BP1 foci, whereas the elimination of FAM135B attenuated these effects. Consistently, our findings revealed that FAM135B could promote homologous recombination and non\u2010homologous end\u2010joining repairs. Further study demonstrated that FAM135B physically bound to the chromodomain of TIP60 and improved its histone acetyltransferase activity. Moreover, FAM135B enhanced the interactions between TIP60 and ATM under resting conditions. Intriguingly, the protein levels of FAM135B dramatically decreased following DNA damage stress but gradually increased during the DNA repair period. Thus, we proposed a potential DDR mechanism where FAM135B sustains a reservoir of pre\u2010existing TIP60\u2010ATM assemblies under resting conditions. Once cancer cells suffer DNA damage, FAM135B is released from TIP60, and the functioning pre\u2010assembled TIP60\u2010ATM complex participates in DDR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>: We characterised FAM135B as a novel DDR regulator and further elucidated the role of the TIP60\u2010ATM axis in response to DNA damage, which suggests that targeting FAM135B in combination with radiation therapy or chemotherapy could be a potentially effective approach for cancer treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.945","type":"journal-article","created":{"date-parts":[[2022,8,18]],"date-time":"2022-08-18T02:54:30Z","timestamp":1660791270000},"source":"Crossref","is-referenced-by-count":12,"title":["FAM135B sustains the reservoir of Tip60\u2010ATM assembly to promote DNA damage response"],"prefix":"10.1002","volume":"12","author":[{"given":"Kai","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital &amp; Institute  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingnan","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing) Laboratory of Molecular Oncology Peking University Cancer Hospital &amp; Institute  Beijing China"},{"name":"Research Unit of Molecular Cancer Research Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenzhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education\/Beijing) Laboratory of 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