MOL/BIO/CH 395J    MOLECULAR BIOLOGY

Spring 2009


Instructors:  

TA:

Lecture Room and Time: 

Class materials

Syllabus

Helpful Hints for Succeeding in 395J 

Note about textbook reading: Most of the figures Dr. Molineux presents in class are in your textbook. Read the material relevant to these figures. If there is extra reading required from the text, we will let you know.


Tues 1-20 Lecture 1:  DNA/RNA structure

Readings: 

Advances in mechanisms of genetic instability related to hereditary neurological diseases

Non-B DNA Conformations, Genomic Rearrangements, and Human Disease

The involvement of non-B DNA structures in gross chromosomal rearrangements

The triple helix: 50 years later, the outcome

Molecular Structure of Nucleic Acids

Z-DNA-forming sequences generate large-scale deletions in mammalian cells

Th 1-22 Lecture 2: DNA/RNA structure continued

Readings:

Base-stacking and base-pairing contributions into thermal stability of the DNA double helix

Supercoiling of DNA <-- A helpful set of notes

DNA TOPOISOMERASES: Structure, Function,and Mechanism
Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Tues 1-27

Lecture 3: DNA Replication

Readings:

Dividing the workload at a eukaryotic replication fork

The Chromosome Replication Machinery of the Archaeon Sulfolobus solfataricus

Replisome mechanics: insights into a twin DNA polymerase machine

Th 1-29 Lecture 4: DNA Replication
Tu 2-3 Lecture 5: DNA Replication and  Replication Initiation,  Bonus Content:  DNA  Repair

Readings: 

DNA replication initiation: mechanisms and regulation in bacteria

Once in a lifetime: strategies for preventing re-replication in prokaryotic and eukaryotic cells
Th 2-5 Lecture 6: DNA Repair 
Tu 2-10 Lecture 7: DNA Repair and Associated Recombination

Readings:

Mechanistic flexibility as a conserved theme across 3 billion years of NHEJ

Paradigms for the Three Rs: DNA Replication, Recombination, and Repair

RNA polymerase: The most specific damage recognition protein in cellular responses to DNA damage?

Transcription-coupled DNA repair: two decades of progress and surprises
Th 2-12 Lecture 8: DNA Recombination

Reading:

Connecting Replication and Recombination

ERROR-PRONE REPAIR DNA POLYMERASES IN PROKARYOTES AND EUKARYOTES

Substrate Specificity of RusA Resolvase Reveals the DNA Structures Targeted by RuvAB and RecG In Vivo

 Unity in transposition reactions

Tu 2-17

Lecture 9: Chromatin Structure

Readings:

Genome-Scale Identification of Nucleosome Positions in S. cerevisiae

X-ray structure of a tetranucleosome and its implications for the chromatin fibre

The DNA-encoded nucleosome organization of a eukaryotic genome

Th 2-19 EXAM I

Key and Grade Spread

Practice Exam

Practice Exam Key

 

Tu 2-24 Lecture 10: Transcription Mechanism

Readings: 

Bacterial RNA Polymerases: The Wholo Story

RNA Polymerase I: A Multifunctional Molecular Machine

A Long Time in the Making— The Nobel Prize for RNA Polymerase

The molecular basis of eukaryotic transcription
Th 2-26 Lecture 11: Transcription Mechanism continued

Readings:

Intrinsic Termination and Anti-termination

Regulatin' RNAP through the Secondary Channel- GreA and B
Tu 3-3


Lecture 12: Prokaryotic Transcription Regulation

Readings:

General Pathway for Turning on Promoters Transcribed by RNA Polymerases Containing Alternative Sigma Factors

How do site-specifc DNA-binding proteins find their targets?

Regulation by destruction: design of the sE envelope stress response


Th 3-5 Lecture 13: Operons and Regulons

 Readings:

Maturation and degradation of RNA in bacteria

Tu 3-10 Lecture 14: Operons and Regulons + RNA Processing

                         
Th 3-12
Exam II

Exam II Key



March 16-20  SPRING BREAK,   Woo Hoo!!
Tu 3-24

Lecture 15: Eukaryotic Transcription machinary

Readings:

Structure and Mechansism of RNAPII Machinery

Factors Involved in Specific Transcription by Mammalian RNA Polymerase II: Role of Transcription Factors IIA, IID, and IIB during Formation of a Transcription-Competent Complex

Structural Basis of Transcription: Separation of RNA from DNA by RNA Polymerase II

Th 3-26

Lecture 16: Eukaryotic transcriptional regulation, chromatin remodeling

Reading:

Regulation of RNA Polymerase II Transcription by Sequence-Specific DNA Binding Factors

Insulators: exploiting transcriptional and epigenetic mechanisms

Transcriptional Activation by Recruitment

Generation and Interconversion of Multiple Distinct Nucleosomal States as a Mechanism for Catalyzing Chromatin Fluidity

Tu 3-31 Lecture 17: RNA processing: Capping, 3´-end formation, RNA editing

Readings:

Molecular Architecture of the Human Pre-mRNA 30 Processing Complex

Pre-mRNA Processing Reaches Back to Transcription and Ahead to Translation

Processing the message: structural insights into capping and decapping mRNA

The RNA world meets behavior:AfiI pre-mRNA editing in animals

RNA editing in regulating gene expression in the brain

Th 4-2 Lecture 18: Pre-mRNA splicing mechanisms, alternative splicing

Readings:

The Spliceosome: Design Principles of a Dynamic RNP Machine

RS domains contact the pre-mRNA throughout spliceosome assembly

Mutually Exclusive Splicing of the Insect Dscam Pre-mRNA Directed by Competing Intronic RNA Secondary Structures

Alternative pre-mRNA splicing: the logic of combinatorial control

Cryo-Electron Microscopy of Spliceosomal Components

Tu 4-7 Lecture 19: Catalytic RNAs: Self-splicing introns and ribozymes

Readings:

The natural history of group I introns

Ribozyme mechanisms and folding

Ribozyme Catalysis of Metabolism in the RNAWorld

Homing endonuclease structure and function

Th 4-9 Lecture 20: RNA transport and localization

Reading:

mRNA Localization: Gene Expression in the Spatial Dimension

Exporting RNA from the nucleus to the cytoplasm

The Glc7p Nuclear Phosphatase Promotes mRNA Export by Facilitating Association of Mex67p with mRNA


From Birth to Death: The Complex Lives of Eukaryotic mRNAs  PLEASE NOTE: You might see an error when opening this paper ("Insufficient data to open the picture" or something like this), please ignore this.  It doesnt pertain to any of the paper information, only the cover page (which you dont need). 
Tu 4-14 Exam III

Practice Exam from 2008 with Key

Exam III Key + Grade Stats 
Th 4-16

Lecture 21: Ribosome structure and assembly

Readings:

The accuracy of ribosomal RNA comparative structure models

Structure and Function of Escherichia coli Ribosomes

An assembly landscape for the 30S ribosomal subunit

Crystal Structure of the Ribosome at 5.5 � Resolution

A hierarchical model for evolution of 23S ribosomal RNA      

Tu 4-21 Lecture 22: Translation: Initiation and control

Readings:

Where to begin? The mechanism of translation initiation codon selection in eukaryotes

Structural and mechanistic insights into hepatitis C viral translation initiation

Complex Riboswitches

Th 4-23

Lecture 23: Translation: Elongation and termination

Reading:

Trans-Translation: The tmRNA-Mediated Surveillance Mechanism for Ribosome
Rescue, Directed Protein Degradation, and Nonstop mRNA Decay


A structural understanding of the dynamic ribosome machine
Tu 4-28 Lecture 24: Eukaryotic RNA Turnover

Readings:

The enzymes and control of eukaryotic mRNA turnover

Quality control of eukaryotic mRNA: safeguarding cells from abnormal mRNA function.

X-ray structure and activity of the yeast Pop2 protein: a nuclease subunit of the mRNA deadenylase complex

Ccr4p is the catalytic subunit of a Ccr4p/Pop2p/Notp mRNA deadenylase complex in Saccharomyces
cerevisiae

Th 4-30 Lecture 25: Protein turnover

Readings:

PROTEASOMES AND THEIR KIN: PROTEASES IN THE MACHINE AGE

Back to the Future with Ubiquitin

The N-end rule: Functions, mysteries, uses

Proposed role of ATP in protein breakdown: Conjugation of proteins
with multiple chains of the polypeptide of ATP-dependent
proteolysis

Tu 5-5

LAST LECTURE!!      Lecture 23: Functions of ncRNA in gene expression: siRNA, miRNA and others

Readings:

Potent and specific genetic interference by double-strandedRNA in Caenorhabditis elegans

MicroRNAs: Genomics, Biogenesis, Mechanism, and Function

Origins and Mechanisms of miRNAs and siRNAs

Th 5-7 EXAM IV

Practice Exam from 2008 with Key

2009 Key with Stats

 

Mol 190 (Only required for ICMB students, although other 395J students are encouraged to attend) Mon 1:30pm @ MBB 1.210

***Please remember that participation will count toward your grade, so come prepared with questions for the presenters. Also note that we will be keeping attendance.***
 

One thing to note regarding journal club:  Please don't hesitate to site and bring in data from other papers that may strengthen the conclusions of the core paper. It is useful to see that other scientists may reach the same results with different experiments.   Additionally, the focus isn't always just the results of the data, but also the experiments themselves.  If interesting or clever experiments were performed, make note of them; they might be useful to all of us.

SCHEDULE:  

DATE PRESENTERS READING
1-26Orginizational Meeting- --------
2-2
Dynamics of DNA replication loops reveal temporal
control of lagging-strand synthesis

2-9
Division of Labor at the Eukaryotic Replication Fork

2-16
Sgs1 Helicase and Two Nucleases Dna2 and Exo1 Resect DNA Double-Strand Break Ends
2-23
UmuD and RecA Directly Modulate the Mutagenic Potential of the Y Family DNA Polymerase DinB
3-2
The replisome uses mRNA as a primer
after colliding with RNA polymerase

3-9
Termination Factor Rho and Its
Cofactors NusA and NusG Silence
Foreign DNA in E. coli
3-16

3-23
The DNA-encoded nucleosome organization of a
eukaryotic genome
3-30
A DNA-tethered cleavage probe reveals the path for
promoter DNA in the yeast preinitiation complex
4-6

4-13
Self-Sustained Replication of an RNA enzyme
4-20
Concurrent nucleation of 16S folding and induced fit in
30S ribosome assembly
4-27



Quality control by the ribosome following peptide bond formation
5-4
Docking of the Proteasomal ATPases’
Carboxyl Termini in the 20S Proteasome’s
a Ring Opens the Gate for Substrate Entry