Non-homologous End Joining - Regulation

Regulation

The choice between NHEJ and homologous recombination for repair of a double-strand break is regulated at the initial step in recombination, 5' end resection. In this step, the 5' strand of the break is degraded by nucleases to create long 3' single-stranded tails. DSBs that have not been resected can be rejoined by NHEJ, but resection of even a few nucleotides strongly inhibits NHEJ and effectively commits the break to repair by recombination. NHEJ is active throughout the cell cycle, but is most important during G1 when no homologous template for recombination is available. This regulation is accomplished by the cyclin-dependent kinase Cdk1 (Cdc28 in yeast), which is turned off in G1 and expressed in S and G2. Cdk1 phosphorylates the nuclease Sae2, allowing resection to initiate.

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