生命科学联合中心
学术报告
Title:Learning about genome duplication mechanisms from protein modifications and cancer mutations
Speaker: Xiaolan Zhao, Ph.D.
Molecular Biology Program
Memorial Sloan-Kettering Cancer Center
Time:2018-6-7(周四),13:00 -14:00 pm
Venue:邓佑才报告厅,北京大学金光生命科学大楼
Host:李晴,北大-清华生命科学联合中心
Abstract:
Genome duplication is essential for all life forms, and its deficiencies lead to many types of human diseases, such as chromosomal breakage syndromes, premature aging, and cancers. Faithful duplication of the human genome of three billion base pairs is a challenging process and many steps within are not understood. The yeast system offers great technical advantages, allowing the discoveries of some key mechanisms leading to the assembly of the replication machinery (replisome) and the subsequent new strand synthesis. Building from these findings, we examined how the DNA helicase for unwinding DNA during genome duplication is regulated by protein medication. In addition, we investigated the roles of the DNA polymerase epsilon (Pol ε), a key member of the replication machinery and a newly defined tumor suppressor. We found that cancer-associated mutations at a highly conserved domain of the Pol ε impair replisome assembly and progression and generate specific forms of genomic instability. These findings shed lights on how DNA helicase must be timely regulated, how polymerase functions in multiple steps of genome duplication, and how perturbing these functions can promote tumorigenesis in humans.