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. 2012 Jul 5;8(7):e1002817. doi: 10.1371/journal.pgen.1002817

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Qu et al.

This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.

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In step 1, DSB formation induces the phosphorylation of H2A (γ-H2A) on surrounding chromatin. Upon DSB resection, Rad3 and 9-1-1 are recruited to single-stranded DNA and single-strand/double-strand junction, respectively. Rad4/Cut5 is also recruited via binding to Rad9. In step 2, through its interactions with modified histones and Rad4/Cut5, Crb2 relocalizes to the DSB and becomes phosphorylated at the SQ/TQ cluster by Rad3. In step 3, phosphorylated SQ/TQ cluster interacts with Chk1 and promotes its phosphorylation by Rad3. In step 4, the activated Chk1 molecule leaves the DSB to fulfill its effector function and allows further rounds of Chk1 activation to occur.