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

为了阐明GANP与AID相互作用在B细胞产生抗体亲和力成熟过程中的分子机制，从人B细胞系Ramos细胞核提取液中鉴定了GANP相互作用蛋白。GANP通过GANP的HAT结构域与组蛋白相互作用，通过乙酰化诱导染色质修饰。GANP与重排的IGV区结合。在IGV转录过程中，这个位置是松弛的。在IGV转录过程中，转录复合体也同样保留，这可能保持了DNA的构型以供延续，并为AID的加入提供了机会。GANP将AID招募到重排的IGV区域的选择性位置，以增加突变频率。我们进一步阐明了GANP在免疫球蛋白基因AID致DNA损伤后DNA修复途径选择中的作用。GANP主要参与在抗体亲和力成熟过程中维持DNA和基因组完整性，以实现有效的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.