Work

Kinase-dependent structural role of DNA-PKcs during immunoglobulin class switch recombination

Year: 2018

Type: article

Abstract: Significance To combat pathogens, B lymphocytes switch the types of antibody they express through a DNA break and repair event termed class switch recombination (CSR). To do so, DNA breaks introduced in specific genomic regions within the antibody gene locus are joined together by the nonhomologous end-joining (NHEJ) DNA repair pathway. Here, we show that mutation and deletion in one NHEJ factor, the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs), leave different molecular signatures at the CSR junctions, uncovering activation-dependent structural function of DNA-PKcs in DNA repair and antibody maturation.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1808490115

Authors: Jennifer L. Crowe, Zhengping Shao, Xiaobin S. Wang, Pei-Chi Wei, Wenxia Jiang, Brian J. Lee, Verna M. Estes, Frederick W. Alt, Shan Zha

Institutions: Columbia University, Boston Children's Hospital, Howard Hughes Medical Institute, Harvard University, Columbia University Irving Medical Center, Herbert Irving Comprehensive Cancer Center

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Howard Hughes Medical Institute, Leukemia and Lymphoma Society, Charles A. King Trust, National Institutes of Health, National Cancer Institute, National Institute of Allergy and Infectious Diseases, National Center for Advancing Translational Sciences

Awards: DNA double-strand break repair, chromosome translocations and cancer, G242601607, G3523978529, G3770854173, Clinical and Translational Science Award, G4130065314, G524649420, G591678259, G7585000060, AID Targeting Mechanisms for IgH Switch Recombination and Somatic Hypermutation

OpenAlex ID: W2887233395

FWCI: 1.067

Cites: 50

Cited by: 29

Related to: 10