日　　時：2024年5月2日　16:00-17:30

開催方法： オンサイト（生命科学総合研究棟B棟301）及びZoomを使用したハイブリッド形式

参加登録URL: https://forms.office.com/r/meLEF9S1Ag

講　　師：本多賢吉（Honda Masayoshi）, Ph.D.
　　　　　Research Associate, University of Iowa.

演　　題：Human RAD52 remodels replication forks restricting fork reversal

要　　旨：
Human RAD52 is a multifunctional DNA repair protein involved in several cellular events that support genome stability including protection of stalled DNA replication forks from excessive degradation. In its gatekeeper role, RAD52 binds to and stabilizes stalled replication forks during replication stress protecting them from reversal by SMARCAL1. 　　　　The structural and molecular mechanism of the RAD52-mediated fork protection remains elusive. Here, biochemical and single-molecule FRET analyses show that RAD52 dynamically remodels replication forks through its strand exchange activity. The presence of the ssDNA binding protein RPA at the fork modulates the kinetics of the strand exchange without impeding the reaction outcome. Mass photometry and single-particle cryo-electron microscopy show that the replication fork promotes a unique nucleoprotein structure containing head-to-head arrangement of two undecameric RAD52 rings with an extended positively charged surface that accommodates all three arms of the replication fork. We propose that the formation and continuity of this surface is important for the strand exchange reaction and for competition with SMARCAL1. Future applicational development of single-molecule FRET technologies toward better understanding macromolecules-DNA interaction will be also discussed.

主　催︓東京大学定量生命科学研究所
共　催︓ERATO胡桃坂クロマチンアトラスプロジェクト