title: Opinion: uracil DNA glycosylase (UNG) plays distinct and non-canonical roles in somatic hypermutation and class switch recombination.
abstract: Activation-induced cytidine deaminase (AID) is essential to class switch recombination (CSR) and somatic hypermutation (SHM). Uracil DNA glycosylase (UNG), a member of the base excision repair complex, is required for CSR. The role of UNG in CSR and SHM is extremely controversial. AID deficiency in mice abolishes both CSR and SHM, while UNG-deficient mice have drastically reduced CSR but augmented SHM raising a possibility of differential functions of UNG in CSR and SHM. Interestingly, UNG has been associated with a CSR-specific repair adapter protein Brd4, which interacts with acetyl histone 4, γH2AX and 53BP1 to promote non-homologous end joining during CSR. A non-canonical scaffold function of UNG, but not the catalytic activity, can be attributed to the recruitment of essential repair proteins associated with the error-free repair during SHM, and the end joining during CSR.
authors.affiliation: Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Ashraf S
authors.initials: AS
authors.lastname: Yousif
authors.affiliation: Laboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
authors.forename: Andre
authors.initials: A
authors.lastname: Stanlie
authors.affiliation: Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Nasim A
authors.initials: NA
authors.lastname: Begum
authors.affiliation: Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan honjo@mfour.med.kyoto-u.ac.jp.
authors.forename: Tasuku
authors.initials: T
authors.lastname: Honjo
mesh_terms: D000818:Animals; D002384:Catalysis; D003564:Cytidine Deaminase / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded; D017578:Immunoglobulin Class Switching; D051379:Mice; D027041:Somatic Hypermutation, Immunoglobulin; D051981:Uracil-DNA Glycosidase / Q000235:genetics / Q000378:metabolism*; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D051981:Uracil-DNA Glycosidase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase
keywords: AID; Brd4; CSR; NHEJ; SHM; UNG