Orchestration of the DNA-Damage Response by the RNF8 Ubiquitin Ligase

The cell response to DNA-damage is manipulated by phosphorylation of MDC1 and the RNF8 ubiquitin ligase. N. K. Kolas, J. R. Chapman and S. Nakada from the Samuel Lunenfeld Research Institute in Canada and from the University of Cambridge (UK) discovered that RNF8 is responsible for ubiquitin conjugation and the accumulation of 53BP1 and BRCA1 at locations of DNA-damage.

The scientists state that MDC1 recruits RNF8 by phosphor-dependent interactions between the forkhead-associated domain of RNF8 and motifs in MDC1 that are phosphorylated by ATM (a protein kinase activated upon DNA-damage). Furthermore, the depletion of E2 enzyme UBC13 impairs the recruitment of 53BP1 to damaged DNA, which points at a cooperation with RNF8. The researchers also observed that RNF8 promotes the G2/M DNA damage checkpoint and enhances resistance to ionising radiation. Recruiting of MDC1, 53BP1 and BRCA1 to sites of DNA double-strand breaks has been observed before, but the mechanism of how the DNA-damage response is orchestrated by ATM-dependent phosphorylation of MDC1 and RNF8-mediated ubiquitination has been unsolved until now.

Related antibodies at antibodies-online.com:

MDC1 (Mediator of DNA Damage Checkpoint Protein 1)

53BP1

53BP1 (p53-binding Protein 1)

BRCA1

RNF8

ATM (ataxia telangiectasia mutated)

Ubiquitin

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