Mechanism of DNA resection during intrachromosomal recombination and immunoglobulin class switching

作者：Bothmer Anne; Rommel Philipp C; Gazumyan Anna; Polato Federica; Reczek Colleen R; Muellenbeck Matthias F; Schaetzlein Sonja; Edelmann Winfried; Chen Phang Lang; Brosh Robert M Jr; Casellas Rafael; Ludwig Thomas; Baer Richard; Nussenzweig Andre; Nussenzweig Michel C; Robbiani Davide F^*

来源：Journal of Experimental Medicine, 2013, 210(1): 115-123.

DOI：10.1084/jem.20121975

DNA double-strand breaks (DSBs) are byproducts of normal cellular metabolism and obligate intermediates in antigen receptor diversification reactions. These lesions are potentially dangerous because they can lead to deletion of genetic material or chromosome translocation. The chromatin-binding protein 53BP1 and the histone variant H2AX are required for efficient class switch (CSR) and V(D)J recombination in part because they protect DNA ends from resection and thereby favor nonhomologous end joining (NHEJ). Here, we examine the mechanism of DNA end resection in primary B cells. We find that resection depends on both CtBP-interacting protein (CtIP, Rbbp8) and exonuclease 1 (Exo1). Inhibition of CtIP partially rescues the CSR defect in 53BP1- and H2AX-deficient lymphocytes, as does interference with the RecQ helicases Bloom (Blm) and Werner (Wrn). We conclude that CtIP, Exo1, and RecQ helicases contribute to the metabolism of DNA ends during DSB repair in B lymphocytes and that minimizing resection favors efficient CSR.

• 出版日期2013-1-14