Molecular mechanism of the selective AID targeting at the IgV-region

为了阐明GANP与AID相互作用在B细胞中产生抗体亲和力成熟的分子机制，在来自人B细胞系拉莫斯细胞的核提取物中鉴定GANP相互作用蛋白。GANP与组蛋白相互作用并通过GANP HAT结构域诱导具有乙酰化的染色质修饰。GANP与重排的IgV区域结合。该位置在IgV转录期间是松弛的。转录复合物在IgV转录期间类似地保留，这可能维持DNA构型以供延续并提供AID加入的机会。GANP将AID募集到重排的IgV区域的选择性位点，以增加突变频率。我们进一步阐明了GANP在AID在IgV区基因引起DNA损伤后DNA修复途径选择中的作用。GANP基本上涉及DNA和基因组完整性的维持，以在抗体亲和力成熟期间进行有效的DNA突变。

To elucidate the molecular mechanism of GANP interacted with AID in generation of antibody affinity maturation in B cells, GANP interacting proteins was identified in the nuclear extract from human B cell line Ramos cells. GANP interacts with histones and induces chromatin modification with the acetylation though the GANP HAT domain. GANP binds to the rearranged IgV region. This position is relaxed during IgV transcription. Transcription complex similarly retains during the IgV transcription, which presumably maintains the DNA configuration for continuation and providing the opportunity of AID accession. GANP recruits AID towards the selective site of the rearranged IgV region to augment mutation frequency. We further clarified the role of GANP in the choice of DNA repair pathways after the DNA injury caused by AID at the IgV region gene. GANP is essentially involved in maintenance of DNA and the genome integrity for efficient DNA mutations during antibody affinity maturation.