MDC1 is ubiquitylated on its tandem BRCT domain and directly binds RAP80 in a UBC13-dependent manner
Copyright policy )MDC1 is ubiquitylated on its tandem BRCT domain and directly binds RAP80 in a UBC13-dependent manner
The cellular response to DNA damage is essential for maintenance of genomic stability. MDC1 is a key member of the DNA damage response. It is an adaptor protein that binds and recruits proteins to sites of DNA damage, a crucial step for a proper response. MDC1 contains several protein-protein interacting modules, including a tandem BRCT domain that mediates various interactions involving MDC1. Here we demonstrate that MDC1 binds directly to RAP80, which is a DNA damage response protein that recruits BRCA1 to sites of damage. The interaction between MDC1 and RAP80 requires the tandem BRCT domain of MDC1 and the ubiquitin-interacting motifs of RAP80. Moreover, the interaction depends on UBC13, an E2 ubiquitin ligase that catalyzes K63-linked poly-ubiquitin chain formation. The results highly propose that the interaction between MDC1 and RAP80 depends on a ubiquitylation event, which we found to take place on K-1977 of MDC1. This study provides the first evidence that interactions involving MDC1 can be regulated by ubiquitylation.
BRCA1 Protein, Lysine, Ubiquitination, Nuclear Proteins, Cell Cycle Proteins, Protein Structure, Tertiary, DNA-Binding Proteins, HEK293 Cells, Multiprotein Complexes, Ubiquitin-Conjugating Enzymes, Trans-Activators, Humans, Histone Chaperones, Protein Interaction Domains and Motifs, Carrier Proteins, Adaptor Proteins, Signal Transducing, DNA Damage, Protein Binding, Sequence Deletion
BRCA1 Protein, Lysine, Ubiquitination, Nuclear Proteins, Cell Cycle Proteins, Protein Structure, Tertiary, DNA-Binding Proteins, HEK293 Cells, Multiprotein Complexes, Ubiquitin-Conjugating Enzymes, Trans-Activators, Humans, Histone Chaperones, Protein Interaction Domains and Motifs, Carrier Proteins, Adaptor Proteins, Signal Transducing, DNA Damage, Protein Binding, Sequence Deletion
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