Orthogonal views of a ribbon diagram of two molecules of Bacillus halodurans RNAse H (silver & green) bound to an RNA (magenta)-DNA (blue) hybrid. Also shown are the side chain carboxylates in the active site (red balls-and-sticks) that chelate two Mg2+ ions (yellow spheres) that participate in catalysis. See: Nowotny M, et al. (2005) Cell 121: 1005-1016.
S. Linn, D. Rio & J. Thorner, instructors
The goal of MCB 200 is to provide an in-depth survey and critical evaluation of the present state of knowledge in molecular biology and cellular biochemistry, using examples from both prokaryotic and eukaryotic cells. Thorough understanding of biochemistry and molecular biology is a prerequisite for enrolling in this course (i.e., completion of the equivalent of the MCB 100A-100B-110 series). There are no required textbooks; instead, each lecture will be accompanied by an extensive bibliography, illustrative handouts, and papers from the primary research literature. In addition to the lectures, there are also weekly class periods (discussion sessions), held each Friday, at which key articles from the primary research literature will be discussed in depth. Each instructor will administer a written examination following the completion of his section of the course.
Enrollment in this course is limited to 45 total and is restricted to MCB graduate students. If space permits, graduate students from other departments or graduate groups may be admitted to the course (first preference will be given to those rotating or working in the laboratories of MCB faculty) and must receive formal consent of the instructor-of-record (Thorner). No auditors are permitted in the Discussion Sections.
Visualization by atomic force microscopy (AFM) of the initial synapsis promoted by purified GTP-bound P-element transposase of the two ends of a P element in DNA (a 629-bp P element flankied at each end by 300 and 600 bp, respectively) into a pre-cleavage complex (loop with two tails of different lengths). See: Tang M, et al. (2005) Genes Dev. 19: 1422-1425.
Positions (yellow) of the residues (A91 and R127) altered in mutants that affect the function of a Ran-binding doman (RBD)-containing protein (Yrb1, the yeast ortholog of RanBP1) have been modeled in ball-and-stick format onto a ribbon diagram of a complex between Ran (blue) bound to a non-hydrolyzable GTP analog (red) and the first RBD in another RBD-containing protein, human nucleoporin NUP358 (cyan). See: Vetter IR, et al. (1999) Nature 398: 39-46.
Lectures: Tuesdays & Thursdays, 12:30 - 2:00 PM
Location: Room 200, Wheeler Hall
Discussion Sections: Fridays* 2:00 - 3:00 PM
3:00 - 4:00 PM103 GPB
103 GPB*Unless otherwise arranged to accommodate the disruption due to the Thanksgiving holiday.
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FACULTY INSTRUCTORS:
PART 1 (Aug. 28 - Sept. 27)
Exam 1: Mon Oct. 1, 6:00 - 8:30 pm
2040 VLSBProf. Stu Linn
422 Barker Hall
Office Hours: Fridays, 4-5 PMslinn@socrates.berkeley.edu
642-7583PART 2 (Oct. 2 - Nov. 1)
Exam 2: Mon Nov. 5, 6:00 - 8:30 pm
2040 VLSBProf. Donald C. Rio
81 Koshland Hall
Office Hours: Fridays, 4-5 PMdon_rio@berkeley.edu
642-1071PART 3 (Nov. 6 - Dec. 11)
Exam 3: Wed Dec. 19, 12:30 - 3:30 pm Room TBAProf. Jeremy W. Thorner
526 Barker Hall
Office Hours: Fridays, 4-5 PMjthorner@berkeley.edu
642-2558
Left, A "cut-away" view of the five-subunit (A-E) RFC (colored)-PCNA (silver)-DNA complex (for clarity, the AAA + modules have been removed from the RFC subunits in the foreground) showing the tracking of the DNA duplex (green & orange) with the N-terminal ends of the clamp-interacting (a4) and central (a5) helices (in yellow) of each subunit.
Middle, View of the RFC-PCNA-DNA model looking down the barrel of the helix (for clarity, the collar of RFC has been removed) and a potential exit path for the 5'-end of the template strand is indicated by green spheres.
Right, Schematic representation of the model of the RFC-PCNA-DNA ternary complex. Alignment of RFC-A with the minor groove of the double helix positions the 5'-terminus of the template strand near the opening between RFC-E and RFC-A.
See: Bowman GD, et al. (2004) Nature 429: 724-730.
READING:
All assigned reading is available on-line from any computer on campus, as well as provided as full-color PDFs at the course website. Some instructors may prepare a bound Reader.EXTRA HANDOUTS:
If you miss a lecture and need a copy of any handouts that were distributed at that class, please go to the wood-and-Plexiglass racks outside of 422 Barker (Linn) or outside of 522 Barker (Thorner & Rio).METHODS BOOK:
Progress in science is often catalyzed by advances in methodology. Moreover, graduate students need to be conversant with the techniques of biochemistry and molecular biology that they will encounter during the course of their dissertation research. For this reason, the instructors in this course have prepared a Methods Book. The present edition of the MCB 200 Methods Book will be available from Krishna Copy Center, at 2111 University Avenue (between Oxford and Shattuck) beginning Friday August 17 and will cost approximately $29.00.STEREOGLASSES:
For viewing stereo images of structures, stereo viewing glasses are useful (especially if you can't cross your eyes to look at such images). Stereoglasses can be checked out from Kathleen Parsons in 524 Barker, between 9:00 AM - 4:00 PM. Please return the stereoglasses by the end of the course (Monday, December 17th).BACKGROUND READING:
There is no assigned or required textbook for MCB 200. However, if you want to strengthen your background or refresh your memory about particular areas that are covered in this course, you can consult useful resources that include, but are not restricted to, the following books. Most of these texts have been used in the Berkeley undergraduate beginning molecular biology courses at one time or another. We will assume that everyone in this class has already had a course that used one of these books or something comparable. Most of these books should be on reserve in the Biosciences Library in VLSB, if you need to brush up on some areas.
- Biochemistry (6th Ed.), Berg JM, Tymoczko JL, Stryer L, W.H. Freeman & Co., New York, NY.
- Biochemistry (3rd Ed.), Voet D, Voet JG, J. Wiley & Sons, New York, NY.
- Lehninger's Principles of Biochemistry (4th Ed.), Nelson, DL, Cox MM, W.H. Freeman & Co., NY, NY.
- DNA Repair and Mutagenesis, Friedberg EC, Walker GC, Siede W, ASM Press, Washington, DC.
- Genes IX, Lewin B, Oxford University Press, New York, NY.
- Cell Biology, Pollard TD, Earnshaw WC, Saunders/Elsevier Science, Philadelphia, PA.
- Molecular Biology of the Cell, (4th Ed.), Alberts B, et al., Garland Science, New York, NY.
- The Cell: A Molecular Approach (4th Ed.), Cooper GM, Hausman RE, Sinauer Associates, Inc., Sunderland, MA.
- Molecular Cell Biology (5th Ed.), Lodish H, et al., W.H. Freeman & Co., New York, NY.
Left, ATP-bound DnaA forms a right-handed helical filament. Side view of four symmetry-related DnaA tetramers are shown. Three domains in each protomer are colored (yellow, red, green); one whole monomer (the initial one in the filament) is colored (silver) to depict a single subunit of the filament.
See: RCSB Protein Data Bank (PDB) ID 2HCB.
Right, Proposed mechanism for origin remodelling by the ATP-DnaA filament. Formation of a positive, toroidal DNA wrap by the ATP-DnaA filament might destabilize the origin by introducing strain into the DNA-unwinding element (DUE) through compensatory negative super-coiling (top panel), which could facilitate DNA melting (bottom-left panel). Coincident with or after opening, the interior of oligomerized ATP-DnaA might directly engage the unwound DUE (bottom-right panel).
See: Mott ML, Berger JM (2007) Nature Rev. Microbiol. 5: 343-354.;
and, Erzberger J, et al. (2006) Nature Struct. Mol. Biol. 13: 676-683.
Last updated: November 5, 2007http://mcb.berkeley.edu/courses/mcb200/index.html
