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Eliezer, Y, Argaman, L, Rhie, A, Doherty, AJ and Goldberg, M (2009) The direct interaction between 53BP1 and MDC1 is required for the recruitment of 53BP1 to sites of damage. J. Biol. Chem. 284:426-35


The DNA damage response mediators, 53BP1 and MDC1, play a central role in checkpoint activation and DNA repair. Here we establish that human 53BP1 and MDC1 interact directly through the tandem BRCT domain of MDC1 and residues 1288-1409 of 53BP1. Following induction of DNA double strand breaks the interaction is reduced, probably due to competition between gamma-H2AX and 53BP1 for the binding of the tandem BRCT domain of MDC1. Furthermore, the MDC1 binding region of 53BP1 is required for focus formation by 53BP1. During mitosis the interaction between 53BP1 and MDC1 is enhanced. The interaction is augmented in a phospho-dependent manner, and the MDC1 binding region of 53BP1 is phosphorylated in vivo in mitotic cells; therefore, it is probably modulated by cell cycle-regulated kinases. Our results demonstrate that the 53BP1-MDC1 interaction per se is required for the recruitment of 53BP1 to sites of DNA breaks, which is known to be crucial for an efficient activation of the DNA damage response. Moreover, the results presented here suggest that the interaction between 53BP1 and MDC1 plays a role in the regulation of mitosis.


PubMed Online version:10.1074/jbc.M807375200


Cell Cycle Proteins/genetics; Cell Cycle Proteins/metabolism; DNA Breaks; HeLa Cells; Histones/genetics; Histones/metabolism; Humans; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/metabolism; Mitosis/physiology; Nuclear Proteins/genetics; Nuclear Proteins/metabolism; Phosphorylation/physiology; Protein Binding/physiology; Protein Structure, Tertiary/physiology; Trans-Activators/genetics; Trans-Activators/metabolism



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


GO:0043517: positive regulation of DNA damage response, signal transduction by p53 class mediator



When MDC1 is knocked down reduced foci formation of DSB DNA repair was observed especially the 53pb1 recruitment. Figure 6B shows the quantitave foci formation 53pb1%. When MDC1 is knocked down, the 53pb1% is greatly reduced which is a known to be involve in DSB DNA repair. This is IMP because of the use of shRNA MDC1 and is this GO because in the presence of MDC1 p53 recruitment to repair foci is increased.


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