Note: the subject headings are also links to their associated readings, listed at the bottom of this page.

DNA Fingerprinting

Segregating genetic markers: Allozymes, RFLPs, Minisatellites or VNTRs, RAPDs, Microsatellites
Applications: evolutionary studies of kinship (lab exercise), forensics, etc.
Mutation and Repair of DNA
Spontaneous mutations
• Sources and spectrums (hotspots), Mutator Genes
• SOS Response (RecA/LexA), Error prone Repair, Inhibition of Cell Division
Transcription-coupled repair and human disease
Mismatch repair, Genetic Stability, and Cancer

Recombination at the Molecular Level

General vs Site-specific Recombination
Double-Strand Break Repair Model - recombination as a repair process
Recombination and gene expression (DNA rearrangements)

• Mating type switching in yeast, antigenic variation in protozoa, flagellar phase variation

Gene Expression and Regulation: A Genetic Switch by M. Ptashne

Review of gene expression - question of developmental controls
Elements involved in control of gene expression

• Transcriptional activators, protein-DNA interactions, protein-protein interactions (two hybrid system)
Regulatory circuits involved in lambda phage gene regulation - examine key experiments
Eukaryotic gene regulation - alternate splicing

Molecular Biology and Medicine

DNA-based diagnosis of genetic diseases
Mapping and cloning human disease genes
• Linkage analysis
• Subtractive Hybridization (DMD)
• Positional Cloning (Cystic Fibrosis)
• Candidate Gene (Marfan Syndrome)
Human gene therapy
Human Genome Project - High resolution maps

Transposable Elements

McClintock - discovered "controlling elements"
E. coli mutations - IS, composite transposons, noncomposite transposons
Mechanisms of Transposition (conservative vs replicative)
Transposable elements in higher organisms
• Ty Elements, Alu repeats, SINES, processed pseudogenes, Retroposons (RNA ---> DNA)

DNA Structure

MBC 98-108: Nice review of DNA as genetic material and basic structural chemistry of nucleic acids. Also helpful if you are a little rusty on notion of genetic code, transcription, translation, etc.

Rec. DNA Chapter 2, 3: Will also serve as a review of the essentials of DNA structure and gene expression.

Watson and Crick Articles: Two original research articles published in 1953 that mark the beginning of the field of molecular biology. Comparable to Darwin's "Origin of the Species" in terms of impact on modern biology, but a lot shorter! Bonus for spotting the error in one of their figures.

The Double Helix (if you have some time to kill): Scandalous autobiographical account of discovery of DNA structure by James Watson. Let me suggest the following chapters to give you a flavor: #2,7,10,12,13,23,25-29, Epilogue.

DNA Packaging

MBC 260-262: DNA topoisomerase activity. Nice diagrams of reaction mechaninsms.

MBC 342-346: Histones and nucleosome structure.

Recombinant DNA Methods

MBC Chapter 7: We will eventually cover most of this chapter on Recombinant DNA Technology, but for now, focus on pp. 291-299 and the DNA cloning section.

Rec. DNA pp. 235-240: Yeast as a model experimental organism. This section will be very relevant to our discussions of the "ARS story" and to our lab projects.

DNA Replicaton - The ARS Story

MBC 251-262: Biochemistry of DNA replication

Series of articles that chronicle the cloning and identification of DNA origins of replication (use study questions as a guide):

1. Stinchcomb et al. (1979) Isolation and characterisation of a yeast chromosomal replicator. Nature 282:39-43.
2. Kearsy (1984) Structural requirements for the function of a yest chromosomal replicator. Cell 37:299-307.
3. Brewer and Fangman (1987) The localization of replication origins on the ARS plasmids in S. cerevisiae. Cell 51:463-471.
4. Bell and Stillman (1992) ATP-dependent recognition of eukaryotic origins of DNA replication by multiprotein complex. Nature 357:128-134.
Rec. DNA p. 158 (fig 9-7 and legend): Good description and diagram of two assays used to identify protein-DNA interactions.