Stephen P. Bell (MIT / HHMI) 2: Single-Molecule Studies of Eukaryotic DNA Replication

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Part 1a: Mechanisms of Chromosomal DNA Replication: The Replication Fork: For an organism to survive, its DNA must be accurately and completely copied during each cell division. Bell explains how replication begins at the DNA replication fork.

Part 1b: Mechanisms of Chromosomal DNA Replication: Initiation of Replication: Bell describes how the multi-enzyme replisome identifies the correct site for the initiation of DNA replication and begins to copy the chromosomal DNA.

Part 2: Single-Molecule Studies of Eukaryotic DNA Replication: Stephen Bell’s lab determined, at the level of single molecules,  the sequence of events which initiate eukaryotic DNA replication.

Talk Overview:
Every time a cell divides, its genomic DNA must be completely, accurately and rapidly duplicated. This feat is completed by an amazing, multi-enzyme nanomachine, called the replisome. The replisome includes one DNA helicase, one RNA polymerase and three DNA polymerases, as well as numerous non-enzymatic proteins, all of which work together at the DNA replication fork. In Part 1a, Dr. Bell gives an excellent, step-by-step description of the function of each replisome protein at the bacterial replication fork.

In Part 1b, Bell focuses on the initiation of DNA replication. At the site where replication begins, chromosomal DNA is separated into two single strands.  Two replisomes are then assembled on the DNA and they move away from each other in opposite directions.  Bell describes how the sites for the initiation of replication are identified, how the helicase is loaded and activated, and how the replisome is assembled.  As he explains, these events are significantly more complicated in eukaryotes than bacteria.

In his last talk, Dr. Bell describes an assay developed in his lab to study eukaryotic DNA replication at the single molecule level. Using this assay, Bell’s lab has determined the detailed process by which eukaryotic DNA helicase loads on DNA and begins the replication process.

Speaker Biography:
Dr. Bell is Professor of Biology at the Massachusetts Institute of Technology and an Investigator of the Howard Hughes Medical Institute.  His lab studies the assembly of multi-protein complexes called replisomes that are responsible for replicating eukaryotic chromosomal DNA, and the regulation of this process to ensure that each chromosome is accurately and completely replicated just once per cell cycle.

In recognition of his contributions to the field, Bell was awarded the National Academy of Sciences Award in Molecular Biology and the ASBMB/Schering-Plough Scientific Achievement Award. Bell has also received the MIT Everett Moore Baker Memorial Teaching Award and the School of Science Teaching Prize for Excellence in Undergraduate Education.  Bell is co-author of the popular Molecular Biology of the Gene textbook.  

Bell received his BA in biochemistry from Northwestern University and his PhD in biochemistry from the University of California, Berkeley where he worked with Robert Tjian. He was a post-doctoral fellow with Bruce Stillman at Cold Spring Harbor Laboratory before moving to MIT.

Learn more about Dr. Bell’s research at his MIT and HHMI sites:
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Thank you Dr. Bell for the obvious time and attention to detail spent on these presentations. Outstanding and inspiring work!

lastchance
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Cell biology, molecular biology, biochemistry, particle physics, quantum field theory...fascinating universe!
Such intricacy for such simpleminded cultural points of view....politics come to mind!
Thanks for educating about the ‘real world’.

garyraab
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Just a small question, sir. Despite one ORC model being the correct one, we see cdc6 loading once for each loading of mcm complex. Is it possible that there is a bit of dna looping such that one ORC can facilitate end to end assembly of mcm requiring cdc6 loading once for each mcm? Thank you for your outstanding work

apurvakmr
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great stuff 🤔nuts and bolts of how we can guide our proteins to build and repair and more so with a high vibration.. nothing is in rest

donysandley
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What a cool complex biological machine. Or more properly, inter-related Molecular Machines. And it was developed by accident, from a pile of mud in the archean age of the world. Not bad for mud.

merlinby