報 告  人: 劉向宇博士（Associate Research Scientist，Department of Pathology, Columbia University）

報告時間：3月21日  上午9:30

報告地點：閔行校區生物藥學樓2-116室

聯 系  人：馮雁 yfeng2009@sjtu.edu.cn

Abstract:

Non-homologous end-joining (NHEJ) is the most prominent DNA double strand break (DSB) repair pathway in mammalian cells. PAXX is the newest NHEJ factor, which shares structural similarity with known NHEJ factors—XRCC4 and XLF. Here we report that PAXX is dispensable for physiological NHEJ in wild-type mice. Yet Paxx-/- mice require XLF and Xlf-/- mice require PAXX for end-ligation. As such, Xlf-/-Paxx-/- mice display severe genomic instability and neuronal apoptosis, which eventually lead to embryonic lethality. Despite their structural similarities, only Xlf-/- cells, but not Paxx-/- cells require ATM/DNA-PK kinase activity for end-ligation. Mechanistically, PAXX promotes the accumulation of KU at DSBs, while XLF enhances LIG4 recruitment without affecting KU dynamics at DNA breaks in vivo. Together these findings identify the molecular functions of PAXX in KU accumulation at DNA ends and reveal distinct, yet critically complementary functions of PAXX and XLF during NHEJ.

個人簡介👨🏽：

       劉向宇博士2002年至2010年就讀於北京大學醫學部基礎醫學專業（八年製本博連讀）生物化學與分子生物學系🪪，獲得博士學位後前往美國紐約哥倫比亞大學醫EON4腫瘤基因研究所（Institute for Cancer Genetics）從事博士後研究工作🧑‍🔧。目前專業技術職位為助理研究科學家（Associate Research Scientist）👼🏽，從事研究方向主要集中於📷：DNA損傷後的非同源末端連接（Non-homologous end joining, NHEJ），同源重組修復(Homologous recombination, HR)以及替代性末端連接（Alternative end joining, A-EJ）的機製研究💂🏿‍♀️，DNA斷端切除（DNA end resection）引起的染色質異位而導致的原癌基因的轉錄激活,基因組穩定性及癌症的發生發展機製，抑癌基因p53的作用機製，CRISPR-Cas9基因編輯動物模型的建立等。這些工作分別以研究文章和綜述的形式發表在國際著名學術刊物PNAS,Mol Cell🪀，Nat Commun🦹🏼‍♂️，Oncotarget,JCB，Cancer Cell等。