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ATM phosphorylates UCHL3. 15 / 16
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"These results suggest that UCHL3 is phosphorylated by ATM following DNA damage."
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"These results suggest that UCHL3 is phosphorylated by ATM following DNA damage."
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"Together, these results suggest that UCHL3 phosphorylation by ATM is important for RAD51 focus formation, HR, and radiosensitivity.Next, we further investigated how UCHL3 phosphorylation affects its function."
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"To test whether UCHL3 could be phosphorylated by ATM/ATR, we examined UCHL3 phosphorylation using an antibody against the consensus of ATM/ATR phosphorylation sites (anti-phospho-SQ/TQ [anti-pSQ/TQ]) following DNA damage."
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"ATM-dependent phosphorylation of the deubiquitinase UCHL3 enables UCHL3 to enhance the retention of Ku80 at damage sites by counteracting Ku80 ubiquitination (Nishi et al., 2018)."
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"In addition, the polyubiquitin chains on the substrate RAD51 can be cleaved by ATM-phosphorylated UCHL3 instead of simulated phosphorylated UCHL3 in vivo."
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"In response to DNA damage, UCHL3 is phosphorylated and activated by ATM, and activated UCHL3 positively regulates HR by deubiquitinating RAD51 to promote the BRCA2-RAD51 interaction ."
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"Mechanistically, in response to DNA damage, the deubiquitinase UCHL3 is phosphorylated and activated by ATM."
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"These results demonstrate that UCHL3 phosphorylation by ATM is important for UCHL3 activation following DNA damage."
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"Additionally, ATM-induced phosphorylation of UCHL3 occurs after DNA damage, which in turn deubiquitinates RAD51 and promotes the binding between BRCA2 and RAD51 ( xref )."
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"Therefore, analyzing the high-resolution crystal structure of the UCHL3 complex bound to K48 tri-Ub or K48 tetra-Ub may further clarify the molecular mechanism by which UCHL3 recognizes and specifically cleaves K48 linkage ubiquitin chains.We know that phosphorylated UCHL3 by ATM can deubiquitinate RAD51 in vivo; however, our studies showed that mimetic phosphorylated UCHL3 can only cleave K48 tri-Ub or longer K48 tetra-Ub with a slower rate in vitro."
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"These results demonstrate that UCHL3 phosphorylation by ATM is important for UCHL3 activation following DNA damage."
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"In addition, phosphorylated UCHL3 by ATM may show excellent hydrolytic properties toward K48 ubiquitin chains compared to wild-type UCHL3."
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"For example, UCHL3 is phosphorylated and activated by ATM following DNA damage, which in turn deubiquitinates RAD51 and promotes the interaction between RAD51 and BRCA2 (Luo et al., 2016)."
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"Together, these results suggest that UCHL3 phosphorylation by ATM is important for RAD51 focus formation, HR, and radiosensitivity."
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