MOLECULAR PATHOLOGY IN DISEASES WITH DNA STRAND BREAKS AND REPAIR DEFECTS.

激活诱导胞苷脱氨酶（activation - induced Cytidine Deaminase， AID）是B细胞中免疫球蛋白类转换的重要分子，AID的突变是II型超igm综合征的主要原因。我们确定了12例日本II型高igm综合征患者。我们发现R190X突变对野生型aids具有显性负向作用。ATM是参与共济失调毛细血管扩张症发病机制的基因，在基因组监测系统中起着重要作用。我们在一例伴有MLL基因重排的急性白血病中发现了种系ATM突变。该突变对野生型ATM也具有显性负向功能，提示ATM功能障碍与儿童白血病MLL基因重排之间存在重要联系。我们发现Ku70/80增加了TCF/ β -连环蛋白依赖的转激活，并正向调节CD23的表达。

Activation-Induce Cytidine Deaminase (AID) is an essential molecule for immunoglobulin class switching in B cells, and the mutation of AID is responsible for hyper-IgM syndrome type II. We identified 12 Japanese patients with hyper-IgM syndrome type II. We found R190X mutation has a dominant negative function against wild type AID.ATM is a gene involved in the pathogenesis of Ataxia Telangiectasia and plays an important role in genome surveillance system. We found germ line ATM mutation in a case with acute leukemia with MLL gene rearrangement. This mutation also had a dominant negative function against wild type ATM, suggesting an important link between ATM dysfunction and MLL gene rearrangement in childhood leukemia. We found Ku70/80 auguments TCF/beta-catenin dependent transactivation and positively regulates CD23 expression.