APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination
Authors
Guikema, Jeroen E. J.Linehan, Erin K.
Tsuchimoto, Daisuke
Nakabeppu, Yusaku
Strauss, Phyllis R.
Stavnezer, Janet
Schrader, Carol E.
UMass Chan Affiliations
Program in Immunology and VirologyDepartment of Molecular Genetics and Microbiology
Document Type
Journal ArticlePublication Date
2007-11-21Keywords
AnimalsB-Lymphocyte Subsets
*DNA Damage
DNA-(Apurinic or Apyrimidinic Site) Lyase
Exodeoxyribonucleases
Gene Expression Regulation
Immunoglobulin Class Switching
Lymphocyte Activation
Mice
Mice, Knockout
Recombination, Genetic
Spleen
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
Antibody class switch recombination (CSR) occurs by an intrachromosomal deletion requiring generation of double-stranded breaks (DSBs) in switch-region DNA. The initial steps in DSB formation have been elucidated, involving cytosine deamination by activation-induced cytidine deaminase and generation of abasic sites by uracil DNA glycosylase. However, it is not known how abasic sites are converted into single-stranded breaks and, subsequently, DSBs. Apurinic/apyrimidinic endonuclease (APE) efficiently nicks DNA at abasic sites, but it is unknown whether APE participates in CSR. We address the roles of the two major mammalian APEs, APE1 and APE2, in CSR. APE1 deficiency causes embryonic lethality in mice; we therefore examined CSR and DSBs in mice deficient in APE2 and haploinsufficient for APE1. We show that both APE1 and APE2 function in CSR, resulting in the DSBs necessary for CSR and thereby describing a novel in vivo function for APE2.Source
J Exp Med. 2007 Nov 26;204(12):3017-26. Epub 2007 Nov 19. Link to article on publisher's siteDOI
10.1084/jem.20071289Permanent Link to this Item
http://hdl.handle.net/20.500.14038/38420PubMed ID
18025127Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1084/jem.20071289