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CtIP-mediated DNA resection is dispensable for IgH class switch recombination by alternative end-joining
Author(s) -
Xiaobin S. Wang,
Junfei Zhao,
Foon Wu-Baer,
Zhengping Shao,
Brian J. Lee,
Olivia M. Cupo,
Raúl Rabadán,
Jean Gautier,
Richard Baer,
Shan Zha
Publication year - 2020
Publication title -
proceedings of the national academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2010972117
Subject(s) - non homologous end joining , endonuclease , recombination , dna , v(d)j recombination , biology , immunoglobulin class switching , microbiology and biotechnology , dna repair , genetics , gene , antibody , b cell
Significance Ig CSR occurs through the nonhomologous end-joining pathway. In NHEJ-deficient cells, substantial CSR can be achieved through the Alt-EJ pathway. High-throughput analyses of IgH CSR junctions in NHEJ-deficient cells show that in contrast to endonuclease-generated breaks, Alt-EJ-mediated CSR can occur without CtIP-mediated DNA resection. The first temporal analyses of CSR junctions in NHEJ-proficient cells further showed that early Sμ internal deletion junctions are enriched for MH. Taken together, the results identified repetitive core IgH switch regions as favorable substrates for MH-mediated recombination independent of resection.

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