Avoiding genomic instability: dna replication, the cell cycle, and cancer

Lectures: 1 session / week, 2 hours / session

Every time a cell divides, it must faithfully duplicate its genetic material once and only once. At the same time, the cell must ensure that this process does not introduce errors that could lead to either cell death or tumorigenesis. In fact, mutations in genes that control DNA replication can be found in a wide variety of tumors. In this class we will learn about how the process of DNA replication is regulated throughout the cell cycle and what happens when DNA replication goes awry. How does the cell know when and where to begin replicating its DNA? How does a cell prevent its DNA from being replicated more than once? How does damaged DNA cause the cell to arrest DNA replication until that damage has been repaired? And how is the duplication of the genome coordinated with other essential processes? We will examine both classical and current papers from the scientific literature to provide answers to these questions and to gain insights into how biologists have approached such problems. We will also learn how the misregulation of DNA replication contributes to tumor formation and how some anti-cancer drugs target proliferating cells by disrupting DNA replication. Finally, we will see how viruses overcome the cellular controls on DNA replication to promote their own multiplication and cause disease.

The primary objective of this course is to provide an introduction to the analysis of the primary scientific literature. This objective will be attained through the in-depth discussion of two research papers each week. With the exception of the first meeting, there will be no formal lectures. Rather, the discussion will be driven by the course participants.

A second objective of this course is to further your understanding of how essential processes are coordinated within the cell cycle. Although we study DNA replication as a specific example of such a process, the principles we learn will be applicable to any cellular process. Thus, we hope that you gain from this course a more integrative understanding of the cell.

This course is pass/fail. Grading is based on in-class participation and completion of two assignments. Attendance at all class meetings is crucial. Any absences must be discussed beforehand with the instructors, and make-up work will be assigned in the case of unavoidable absences.

Each week, we will discuss two scientific articles pertaining to the topic at hand. These papers may be "classic" papers that first described a major concept in the cell-cycle regulation of DNA replication, or they may be more recent papers that solve long-standing mysteries in the field(or introduce new ones!). In any case, the goal of each session will be to learn how to critically interpret data. We will discuss the reasoning behind each of the experiments, the techniques used, and the implications of the results for the fields of DNA replication and cell cycle control. At the end of each class, the instructors will briefly describe the relevant background and techniques necessary to understand the papers being covered during the next class.

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