IA. Mechanisms of Chromosomal DNA Replication: The DNA Replication Fork
IB. Mechanisms of Chromosomal DNA Replication: Initiation of DNA Replication
II. Single-Molecule Studies of Eukaryotic DNA Replication
Part IA. Mechanisms of Chromosomal DNA Replication: The DNA Replication Fork
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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.
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.
- Robert Tjian iBioSeminar: The Molecular Biology of Gene Regulation
- Jim Haber iBioSeminar: Mechanisms of DNA Repair
- Melissa Moore iBioSeminar: RNA Processing
- Carlos Bustamante iBioSeminar: Single Molecule Manipulation in Biochemistry
Ticau, S., Friedman, L. J., Ivica, N. A., Gelles, J., & Bell, S. P. (2015). Single-molecule studies of origin licensing reveal mechanisms ensuring bidirectional helicase loading. Cell, 161(3), 513–525.
Bell, S. P., & Labib, K. (2016). Chromosome Duplication in Saccharomyces cerevisiae. Genetics, 203(3), 1027–1067.
Costa, A., Hood, I. V., & Berger, J. M. (2013). Mechanisms for Initiating Cellular DNA Replication. Annual Review of Biochemistry, 82(1), 25–54.