Mechanism of DNA Sequence Alignment During Homologous Recombination

2019-07-07 00:18:13 0

定量生物学中心

学术报告

 

题目:  Mechanism of DNA Sequence Alignment During Homologous Recombination

报告人:Dr. Zhi Qi

             Department of Biochemistry & Molecular Biophysics, Columbia University, New York, NY

时间:2014-11-5(周三),13:00-14:00

地点:北京大学老化学楼东配楼102会议室

主持人:定量生物学中心,刘峰博士

Abstract

Homologous recombination (HR) promotes the exchange genetic information between different DNA molecules. During HR, members of the RecA/Rad51 family of recombinases must align and pair ssDNA with a homologous dsDNA template, but the physical basis for these early stages of recombination remain largely undefined. Here we use single-molecule imaging to visualize Rad51 as it attempts to align and pair homologous DNA sequences in real-time. We show that Rad51 uses a length-based recognition mechanism while interrogating dsDNA, enabling robust kinetic selection of 8-nucleotide (nt) tracts of microhomology, which confines the search to sites with a high probability of being the homologous target. Successful pairing with a 9th nucleotide coincides with an additional reduction in binding free energy and subsequent strand invasion occurs in precise 3-nt steps, reflecting the unusual base triplet organization of the presynaptic complex. These findings provide crucial new insights into the physical and evolutionary underpinnings of DNA recombination.