Abstract:

DNA mismatch repair (MMR) is renowned as a fundamental guardian of genomic stability, expertly correcting errors that arise during DNA replication. This system is essential for preventing mutations and protecting against diseases like cancer. However, a startling paradox has emerged: this very same repair pathway can be hijacked to drive genomic instability. In the case of inherited Trinucleotide Repeat (TNR) disorders, the normal MMR machinery becomes a primary engine of disease progression. Rather than correcting errors, MMR proteins promote the pathological expansion of repetitive DNA sequences beyond a toxic threshold. This expansion is the root cause of many devastating neurodegenerative diseases, including Huntington’s disease and various spinocerebellar ataxias. This seminar will explore the fascinating paradox of how a protective mechanism transforms into a destructive force, examining the profound implications for understanding and treating these conditions.

Profile

李国民，现任首都医学科学创新中心肿瘤研究所所长; 首都医科大学讲席教授；美国科学促进会（AAAS）会士。分别获武汉大学生物系学士、硕士和美国韦恩州立大学化学系博士学位。在杜克大学Paul Modrich教授（2015年诺贝尔化学奖获得者）实验室从事博士后研究，对该项获奖工作做出重要贡献。2023年回国前，任得克萨斯大学西南医学中心讲席教授、The Reece A. Overcash 肠癌研究中心主任。长期从事DNA错配修复机理研究及其对癌症和神经退行性疾病的发生、发展和治疗的作用，成果发表在Cell、Science、Cancer Cell，Nature Medicine等期刊上。长期担任DNA Repair、Cell Research、Cell Discovery、JBC、Science China Life Sciences （SCLS）、STTT等国内外高水平期刊副主编或编委。