{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Gao SS"],"funding":["Innovative Research Group Project of the National Natural Science Foundation of China","the National Key Basic Research Program (973 Program) of MOST"],"pagination":["eaba7822"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7439314"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["6(28)"],"pubmed_abstract":["Nonhomologous end joining (NHEJ) and homologous recombination (HR) are major repair pathways of DNA double-strand breaks (DSBs). The pathway choice of HR and NHEJ is tightly regulated in cellular response to DNA damage. Here, we demonstrate that the interaction of TIP60 with DNA-PKcs is attenuated specifically in S phase, which facilitates HR pathway activation. SUMO2 modification of TIP60 K430 mediated by PISA4 E3 ligase blocks its interaction with DNA-PKcs, whereas TIP60 K430R mutation recovers its interaction with DNA-PKcs, which results in abnormally increased phosphorylation of DNA-PKcs S2056 in S phase and marked inhibition of HR efficiency, but barely affects NHEJ activity. TIP60 K430R mutant cancer cells are more sensitive to radiation and PARP inhibitors in cancer cell killing and"],"journal":["Science advances"],"pubmed_title":["TIP60 K430 SUMOylation attenuates its interaction with DNA-PKcs in S-phase cells: Facilitating homologous recombination and emerging target for cancer therapy."],"pmcid":["PMC7439314"],"funding_grant_id":["2015CB910601","81530085, 31870847，31800704"],"pubmed_authors":["Liu X","Liu Y","Hu S","Song M","Guan H","Gao SS","Yan S","Zhang S","Zhou PK","Guo ZP","Xie DF"],"additional_accession":[]},"is_claimable":false,"name":"TIP60 K430 SUMOylation attenuates its interaction with DNA-PKcs in S-phase cells: Facilitating homologous recombination and emerging target for cancer therapy.","description":"Nonhomologous end joining (NHEJ) and homologous recombination (HR) are major repair pathways of DNA double-strand breaks (DSBs). The pathway choice of HR and NHEJ is tightly regulated in cellular response to DNA damage. Here, we demonstrate that the interaction of TIP60 with DNA-PKcs is attenuated specifically in S phase, which facilitates HR pathway activation. SUMO2 modification of TIP60 K430 mediated by PISA4 E3 ligase blocks its interaction with DNA-PKcs, whereas TIP60 K430R mutation recovers its interaction with DNA-PKcs, which results in abnormally increased phosphorylation of DNA-PKcs S2056 in S phase and marked inhibition of HR efficiency, but barely affects NHEJ activity. TIP60 K430R mutant cancer cells are more sensitive to radiation and PARP inhibitors in cancer cell killing and","dates":{"release":"2020-01-01T00:00:00Z","publication":"2020 Jul","modification":"2025-04-03T22:39:40.799Z","creation":"2020-08-29T07:24:46Z"},"accession":"S-EPMC7439314","cross_references":{"pubmed":["32832608"],"doi":["10.1126/sciadv.aba7822"]}}