{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Abd El-Hafeez AA"],"funding":["NCATS NIH HHS","NIDDK NIH HHS","NIAID NIH HHS","NHLBI NIH HHS","NCI NIH HHS","NINDS NIH HHS","NIGMS NIH HHS"],"pagination":["105973"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9900518"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(2)"],"pubmed_abstract":["Upon sensing DNA double-strand breaks (DSBs), eukaryotic cells either die or repair DSBs via one of the two competing pathways, i.e., non-homologous end-joining (NHEJ) or homologous recombination (HR). We show that cell fate after DSBs hinges on GIV/Girdin, a guanine nucleotide-exchange modulator of heterotrimeric Giα•βγ protein. GIV suppresses HR by binding and sequestering BRCA1, a key coordinator of multiple steps within the HR pathway, away from DSBs; it does so using a C-terminal motif that binds BRCA1's BRCT-modules via both phospho-dependent and -independent mechanisms. Using another non-overlapping C-terminal motif GIV binds and activates Gi and enhances the \"free\" Gβγ→PI-3-kinase→Akt pathway, which promotes survival and is known to suppress HR, favor NHEJ. Absence of GIV, or loss of either of its C-terminal motifs enhanced cell death upon genotoxic stress. Because GIV selectively binds other BRCT-containing proteins suggests that G-proteins may fine-tune sensing, repair, and survival after diverse types of DNA damage."],"journal":["iScience"],"pubmed_title":["Regulation of DNA damage response by trimeric G-proteins."],"pmcid":["PMC9900518"],"funding_grant_id":["T32 CA121938","R01 CA238042","R33 CA225549","R01 CA238023","R56 NS073976","R01 CA160911","R01 DK107585","T32 CA067754","R01 GM117424","R01 AI118985","R37 CA222563","R01 CA100768","R01 AI141630","R01 NS073976","R01 HL145477","UG3 TR002968","U01 CA210152","R50 CA221807"],"pubmed_authors":["Sun N","Rajapakse N","Luker GD","Abd El-Hafeez AA","Chamarthi P","Hazra TK","Das S","Luker KE","Ghosh P","Roy S","Chakraborty A","Ear J"],"additional_accession":[]},"is_claimable":false,"name":"Regulation of DNA damage response by trimeric G-proteins.","description":"Upon sensing DNA double-strand breaks (DSBs), eukaryotic cells either die or repair DSBs via one of the two competing pathways, i.e., non-homologous end-joining (NHEJ) or homologous recombination (HR). We show that cell fate after DSBs hinges on GIV/Girdin, a guanine nucleotide-exchange modulator of heterotrimeric Giα•βγ protein. GIV suppresses HR by binding and sequestering BRCA1, a key coordinator of multiple steps within the HR pathway, away from DSBs; it does so using a C-terminal motif that binds BRCA1's BRCT-modules via both phospho-dependent and -independent mechanisms. Using another non-overlapping C-terminal motif GIV binds and activates Gi and enhances the \"free\" Gβγ→PI-3-kinase→Akt pathway, which promotes survival and is known to suppress HR, favor NHEJ. Absence of GIV, or loss of either of its C-terminal motifs enhanced cell death upon genotoxic stress. Because GIV selectively binds other BRCT-containing proteins suggests that G-proteins may fine-tune sensing, repair, and survival after diverse types of DNA damage.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Feb","modification":"2026-05-29T03:35:53.764Z","creation":"2025-04-06T19:10:30.024Z"},"accession":"S-EPMC9900518","cross_references":{"pubmed":["36756378"],"doi":["10.1016/j.isci.2023.105973"]}}