APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination
APE1- and APE2-dependent DNA breaks in immunoglobulin class switch recombination
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DOI：
10.1084/jem.20071289
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发表时间：
2007-11-26
影响因子：
15.3
通讯作者：
Schrader, Carol E.
中科院分区：
文献类型：
--
作者：
Guikema, Jeroen E. J.;Linehan, Erin K.;Schrader, Carol E.
抗体类别转换重组（CSR）通过染色体内缺失发生，需要在转换区DNA中产生双链断裂（DSB）。DSB形成的初始步骤已被阐明，包括由激活诱导的胞苷脱氨酶引起的胞嘧啶脱氨基和由尿嘧啶DNA糖基化酶产生的脱碱基位点。然而，目前尚不清楚脱碱基位点如何转化为单链断裂，并随后转化为DSB。脱嘌呤/脱嘧啶核酸内切酶（APE）能有效地在脱碱基位点切割DNA，但APE是否参与CSR尚不清楚。我们解决的两个主要的哺乳动物APE，APE 1和APE 2，在CSR中的作用。APE 1缺陷导致小鼠胚胎死亡;因此，我们研究了APE 2缺陷和APE 1单倍不足小鼠的CSR和DSB。我们表明，APE 1和APE 2的功能在CSR，导致在CSR所需的DSBs，从而描述了一种新的体内功能APE 2。
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.