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4月14日清华大学学术报告 - Jiazhi Hu
发布时间:2016-04-12关键字:

ATM prevents RAG-initiated double-stranded breaks to form dicentric chromosomes that lead to B cell lymphomas


 

 

Dr. Jiazhi Hu

Research Fellow

Program in Cellular and Molecular Medicine,

Boston Children's Hospital


 

ATM is the master kinase responding to DNA double-stranded breaks (DSBs). In the absence of ATM, DSBs can persist and form translocations that participate in tumorigenesis. We generated mouse models recurrently developing B cell lymphomas in the absence of ATM, and found all the tumors arose from dicentric chromosomes involving RAG-generated DSBs in the IgH locus. We employed a high-throughput sequencing method to track DSBs in the ATM-deficient cells, and found ATM DNA damage response pathway could tether broken ends from the same DSBs together to facilitate their re-joining, and thus prevented the forming of translocations including dicentric chromosomes. In addition, we found that the RAG endonuclease, which is essential for V(D)J recombination, could generate numerous “off-target” cleavages in the genome; however, this “off-target” activity was restricted by genome-wide topologically-associated domains (TADs). We further proposed a linear-tracking model of RAG to explain the joining profiles of RAG-initiated DSBs.


Time: 10:00-11:30, Apr. 14th(Thursday)

Venue: D326, Medical Science Building

Host: Dr. Yun-Cai Liu

 

 




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