Single Molecule Enzymology of DNA Replication and Repair

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Sunday, February 21, 2021
8:30 – 10:00 a.m.
On Zoom

As part of the current promotion cycle of the University, Professor Samir Hamdan is being considered for promotion to Full Professor. A requirement of the promotion process is to give a technical promotion colloquium, which is open to the entire University Community.This colloquium will provide interesting insights into the research interests and achievements of Professor Hamdan.

Abstract

The ability of single molecule techniques to track the behavior of individual molecules with excellent spatial (nanometer) and temporal (millisecond) resolution, make these techniques instrumental to studying biological systems. These powerful approaches allow us to observe transient intermediates and elucidate reaction mechanism because they do not require synchronization and are void of ensemble averaging. Specifically, my discipline focuses on single molecule enzymology of biological reactions mediated by large multi-protein complexes, and, in particular, the multiprotein DNA replication machinery (the replisome).My research program employs biochemistry and single-molecule imaging to study the underlying mechanisms of the human replisome. I will discuss our progress towards achieving my ultimate goal to reconstitute the entire human replisome from purified proteins (over 30 proteins) and put KAUST on the map as the place where this system was first reconstituted and characterized. Over the years, I have also focused on making an impact in the DNA repair field through studying how DNA repair nucleases remove toxic intermediary structures that are naturally produced during the repair pathways.I will finally conclude with our future focus on studying the mechanism of two key DNA repair nucleases within the context of the human nucleotide excision repair that removes bulky DNA lesions, such as those produced by UV radiation.

About the speaker

Prof Hamdan has been always interested in understanding the mechanism of the replisome since he started his Ph.D. at the Australian National University, where he solved the crystal structure of the proofreading subunit of the E. coli DNA replicase and characterized its interactions with other proteins. During his postdoctoral studies at Harvard Medical School, he focused on characterizing how bacteriophage T7 replisome coordinates DNA synthesis on leading and lagging strands. There, he moved towards using single molecule imaging as a technology to better understand this complex process. He was the first to reconstitute the T7 replisome at the single molecule level and observed its activities in real-time. He joined KAUST as a founding faculty and was promoted to Associate Professor in 2014.Since starting his independent career at KAUST, he has moved into focusing on reconstituting and studying the replisome in the human system. Using single molecule imaging, he continues to contribute towards creating a detailed mechanistic view of this least-characterized, yet highly relevant, replisome. Among many other contributions to KAUST, he served as the Bioscience Program Chair, Associate Dean of BESE and is currently the Interim Dean of BESE.

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