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The Mre11/Rad50/Nbs1 protein complex plays central enzymatic and signaling roles in the DNA-damage response. Nuclease (Mre11) and scaffolding (Rad50) components of MRN have been extensively characterized, but the molecular basis of Nbs1 function has remained elusive. Here, we present a 2.3Å crystal structure of the N-terminal region of fission yeast Nbs1, revealing an unusual but conserved architecture...
Phosphorylated histone H2AX (“γ-H2AX”) recruits MDC1, 53BP1, and BRCA1 to chromatin near a double-strand break (DSB) and facilitates efficient repair of the break. It is unclear to what extent γ-H2AX-associated proteins act in concert and to what extent their functions within γ-H2AX chromatin are distinct. We addressed this question by comparing the mechanisms of action of MDC1 and 53BP1 in DSB repair...
Checkpoint signaling pathways are of crucial importance for the maintenance of genomic integrity. Within these pathways, the effector kinase Chk1 plays a central role in mediating cell-cycle arrest in response to DNA damage, and it does so by phosphorylating key cell-cycle regulators.By investigating the subcellular distribution of Chk1 by cell fractionation, we observed that around 20% of it localizes...
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