Class Focus, Spring 2007
- Organization Meeting and Rules of Engagement
- Biochemistry and Structure of Replicating Machines at the Protein-DNA Interface
- Molecular Mechanisms of Genomic Information Expansion
- A Revealing Structure of the Exon Junction Complex
Week 1: Introduction and Scheduling
- Slide Zen
- Delivery Zen
- Feel free to add links that help you
Week 2: Rewrite the textbooks on DNA Replication
- Lopes M, Foiani M, and Sogo JM. Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions. Mol Cell. 2006 Jan 6;21(1):15-27. DOI:10.1016/j.molcel.2005.11.015 |
- Heller RC and Marians KJ. Replication fork reactivation downstream of a blocked nascent leading strand. Nature. 2006 Feb 2;439(7076):557-62. DOI:10.1038/nature04329 |
Review: Replisome assembly and the direct restart of stalled replication forks.
Heller RC, & Marians KJ. Nat Rev Mol Cell Biol. 2006 Dec;7(12):932-43. Epub 2006 Nov 8.
BND Cellulose Protocol 
Using Caffeine to Elute Replication Intermediates with Single Stranded Regions 
DNA Replication Slides (pdf)
Chris and Mahta's Slides (ppt)
Supplemental Slides (ppt)
Week 3: Go, Ichi, Nii, and San;New Components of DNA Replication
- Moyer SE, Lewis PW, and Botchan MR. Isolation of the Cdc45/Mcm2-7/GINS (CMG) complex, a candidate for the eukaryotic DNA replication fork helicase. Proc Natl Acad Sci U S A. 2006 Jul 5;103(27):10236-10241. DOI:10.1073/pnas.0602400103 |
Chayne's Intro slides (ppt)
Larry's slides on Moyer (ppt)
Week 4:non-coding RNAs
- Chaumeil J, Le Baccon P, Wutz A, and Heard E. A novel role for Xist RNA in the formation of a repressive nuclear compartment into which genes are recruited when silenced. Genes Dev. 2006 Aug 15;20(16):2223-37. DOI:10.1101/gad.380906 |
- Pollard KS, Salama SR, Lambert N, Lambot MA, Coppens S, Pedersen JS, Katzman S, King B, Onodera C, Siepel A, Kern AD, Dehay C, Igel H, Ares M Jr, Vanderhaeghen P, and Haussler D. An RNA gene expressed during cortical development evolved rapidly in humans. Nature. 2006 Sep 14;443(7108):167-72. DOI:10.1038/nature05113 |
- Ponting CP and Lunter G. Evolutionary biology: human brain gene wins genome race. Nature. 2006 Sep 14;443(7108):149-50. DOI:10.1038/nature05154 |
- Zaratiegui M, Irvine DV, and Martienssen RA. Noncoding RNAs and gene silencing. Cell. 2007 Feb 23;128(4):763-76. DOI:10.1016/j.cell.2007.02.016 |
- Keohane AM, O'neill LP, Belyaev ND, Lavender JS, and Turner BM. X-Inactivation and histone H4 acetylation in embryonic stem cells. Dev Biol. 1996 Dec 15;180(2):618-30. DOI:10.1006/dbio.1996.0333 |
- Heard E and Disteche CM. Dosage compensation in mammals: fine-tuning the expression of the X chromosome. Genes Dev. 2006 Jul 15;20(14):1848-67. DOI:10.1101/gad.1422906 |
- O'Neill MJ. The influence of non-coding RNAs on allele-specific gene expression in mammals. Hum Mol Genet. 2005 Apr 15;14 Spec No 1:R113-20. DOI:10.1093/hmg/ddi108 |
- Avner P and Heard E. X-chromosome inactivation: counting, choice and initiation. Nat Rev Genet. 2001 Jan;2(1):59-67. DOI:10.1038/35047580 |
- Seward DJ, Cubberley G, Kim S, Schonewald M, Zhang L, Tripet B, and Bentley DL. Demethylation of trimethylated histone H3 Lys4 in vivo by JARID1 JmjC proteins. Nat Struct Mol Biol. 2007 Mar;14(3):240-2. DOI:10.1038/nsmb1200 |
- Diaz-Perez SV, Ferguson DO, Wang C, Csankovszki G, Wang C, Tsai SC, Dutta D, Perez V, Kim S, Eller CD, Salstrom J, Ouyang Y, Teitell MA, Kaltenboeck B, Chess A, Huang S, and Marahrens Y. A deletion at the mouse Xist gene exposes trans-effects that alter the heterochromatin of the inactive X chromosome and the replication time and DNA stability of both X chromosomes. Genetics. 2006 Nov;174(3):1115-33. DOI:10.1534/genetics.105.051375 |
- Chow JC, Yen Z, Ziesche SM, and Brown CJ. Silencing of the mammalian X chromosome. Annu Rev Genomics Hum Genet. 2005;6:69-92. DOI:10.1146/annurev.genom.6.080604.162350 |
Nature podcast on Pollard paper
Summary ppt of Chaumeil, et al
X Inactivation Intro Slides
Week 5: Consolidating weeks 2, 3 and 4 (Wed May 2 10AM)
Review of Methods/papers, answering questions from non-coding RNA and DNA Replication papers
Week 6: Student Research Forum
Week 7: Nucleosome positioning and Chromatin Structure
- Richmond TJ. Genomics: predictable packaging. Nature. 2006 Aug 17;442(7104):750-2. DOI:10.1038/442750a |
- Kiyama R and Trifonov EN. What positions nucleosomes?--A model. FEBS Lett. 2002 Jul 17;523(1-3):7-11.
- link to Eran Segal's Lab page where you can test your favorite sequence for predicted nucleosome occupancy
Nucleosome Coding Introduction
Nucleosome Coding Paper
Nucleosome Coding- student Q&A
Week 8: Structure function of DNA Helicases
- Enemark EJ and Joshua-Tor L. Mechanism of DNA translocation in a replicative hexameric helicase. Nature. 2006 Jul 20;442(7100):270-5. DOI:10.1038/nature04943 |
- Eichman BF and Fanning E. The power of pumping together; deconstructing the engine of a DNA replication machine. Cell. 2004 Oct 1;119(1):3-4. DOI:10.1016/j.cell.2004.09.023 |
- Gai D, Zhao R, Li D, Finkielstein CV, and Chen XS. Mechanisms of conformational change for a replicative hexameric helicase of SV40 large tumor antigen. Cell. 2004 Oct 1;119(1):47-60. DOI:10.1016/j.cell.2004.09.017 |
- Hanson PI and Whiteheart SW. AAA+ proteins: have engine, will work. Nat Rev Mol Cell Biol. 2005 Jul;6(7):519-29. DOI:10.1038/nrm1684 |
:PCNA, the Maestro of the Replication Fork []
A recent addition to Cell that looks at a critical component of the replication fork.
- Cozzarelli NR, Cost GJ, Nöllmann M, Viard T, and Stray JE. Giant proteins that move DNA: bullies of the genomic playground. Nat Rev Mol Cell Biol. 2006 Aug;7(8):580-8. DOI:10.1038/nrm1982 |
Week 9: A gripping story about the RNA exon junction complex
- Bono F, Ebert J, Lorentzen E, and Conti E. The crystal structure of the exon junction complex reveals how it maintains a stable grip on mRNA. Cell. 2006 Aug 25;126(4):713-25. DOI:10.1016/j.cell.2006.08.006 |
- Link to Schedule Page and Questions/Comments[]
- Tange TØ, Nott A, and Moore MJ. The ever-increasing complexities of the exon junction complex. Curr Opin Cell Biol. 2004 Jun;16(3):279-84. DOI:10.1016/j.ceb.2004.03.012 |
- Andersen CB, Ballut L, Johansen JS, Chamieh H, Nielsen KH, Oliveira CL, Pedersen JS, Séraphin B, Le Hir H, and Andersen GR. Structure of the exon junction core complex with a trapped DEAD-box ATPase bound to RNA. Science. 2006 Sep 29;313(5795):1968-72. DOI:10.1126/science.1131981 |
- Stroupe ME, Tange TØ, Thomas DR, Moore MJ, and Grigorieff N. The three-dimensional arcitecture of the EJC core. J Mol Biol. 2006 Jul 21;360(4):743-9. DOI:10.1016/j.jmb.2006.05.049 |
- Shibuya T, Tange TØ, Sonenberg N, and Moore MJ. eIF4AIII binds spliced mRNA in the exon junction complex and is essential for nonsense-mediated decay. Nat Struct Mol Biol. 2004 Apr;11(4):346-51. DOI:10.1038/nsmb750 |
- Ballut L, Marchadier B, Baguet A, Tomasetto C, Séraphin B, and Le Hir H. The exon junction core complex is locked onto RNA by inhibition of eIF4AIII ATPase activity. Nat Struct Mol Biol. 2005 Oct;12(10):861-9. DOI:10.1038/nsmb990 |
- Shi H and Xu RM. Crystal structure of the Drosophila Mago nashi-Y14 complex. Genes Dev. 2003 Apr 15;17(8):971-6. DOI:10.1101/gad.260403 |
- Cordin O, Banroques J, Tanner NK, and Linder P. The DEAD-box protein family of RNA helicases. Gene. 2006 Feb 15;367:17-37. DOI:10.1016/j.gene.2005.10.019 |
Link to Schedule page:
BMCB625:Exon Jxn Complex
Week 10: Individual Presentations
Chris - Papers
Outline of Talk and Discussion
- Introduction: Perspectives between disciplines and establishing common languages
- "Classic Paper" (as reference): Luria and Delbruck Fluctuation Test, trends via statistical arguements
- "Main Paper" : Lactose Utilization as a model for Bistability
- MAIN PAPER: "Multistability in the lactose utilization network of Escherichia coli"
EM Ozbudak, et al,
Nature 427, 737-740 (19 February 2004)
- CLASSIC: "Mutations of Bacteria from Virus Sensitivity to Virus Resistance"
S. E. Luria and M. Delbrück,
Genetics. 1943 November; 28(6): 491–511
- See Below: "Biologists Fixing Radios"
- Presentation: Presentation
Chris - Bonus Materials
A good primer on how biologists and engineers look at a problem in different ways; while many comments do not address the complexity of biochemistry and genetics, it does provide an interesting perspective on what we consider "important." Also, of importance, in my opinion, is developing a common language by which numerous disciplines can communicate. I'll touch more on this particular topic during my talk.
Y. Lazebnik, "Can a Biologist Fix a Radio? or, What I Learned while Studying Apoptosis"
Bio fixing Radios
Chayne - Papers
DNA Gyrase ppt lecture (Nollmann, et al.)
- Nöllmann M, Stone MD, Bryant Z, Gore J, Crisona NJ, Hong SC, Mitelheiser S, Maxwell A, Bustamante C, and Cozzarelli NR. Multiple modes of Escherichia coli DNA gyrase activity revealed by force and torque. Nat Struct Mol Biol. 2007 Apr;14(4):264-71. DOI:10.1038/nsmb1213 |
Chayne - Bonus Materials
- Maxwell A, Costenaro L, Mitelheiser S, and Bates AD. Coupling ATP hydrolysis to DNA strand passage in type IIA DNA topoisomerases. Biochem Soc Trans. 2005 Dec;33(Pt 6):1460-4. DOI:10.1042/BST20051460 |
- Schoeffler AJ and Berger JM. Recent advances in understanding structure-function relationships in the type II topoisomerase mechanism. Biochem Soc Trans. 2005 Dec;33(Pt 6):1465-70. DOI:10.1042/BST20051465 |
- Corbett KD and Berger JM. Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases. Annu Rev Biophys Biomol Struct. 2004;33:95-118. DOI:10.1146/annurev.biophys.33.110502.140357 |
- Gellert M, Mizuuchi K, O'Dea MH, and Nash HA. DNA gyrase: an enzyme that introduces superhelical turns into DNA. Proc Natl Acad Sci U S A. 1976 Nov;73(11):3872-6.
- Espeli O and Marians KJ. Untangling intracellular DNA topology. Mol Microbiol. 2004 May;52(4):925-31. DOI:10.1111/j.1365-2958.2004.04047.x |
- Wasserman SA and Cozzarelli NR. Biochemical topology: applications to DNA recombination and replication. Science. 1986 May 23;232(4753):951-60.
- Nöllmann M, Crisona NJ, and Arimondo PB. Thirty years of Escherichia coli DNA gyrase: from in vivo function to single-molecule mechanism. Biochimie. 2007 Apr;89(4):490-9. DOI:10.1016/j.biochi.2007.02.012 |
- Nicholas Cozzarelli (1938-2006) obituary in Cell----
Week 11: Individual Presentations
Mahta - Papers
- Christov CP, Gardiner TJ, Szüts D, and Krude T. Functional requirement of noncoding Y RNAs for human chromosomal DNA replication. Mol Cell Biol. 2006 Sep;26(18):6993-7004. DOI:10.1128/MCB.01060-06 |
Mahta -Bonus Materials
- Chen X and Wolin SL. The Ro 60 kDa autoantigen: insights into cellular function and role in autoimmunity. J Mol Med (Berl). 2004 Apr;82(4):232-9.
- Green CD, Long KS, Shi H, and Wolin SL. Binding of the 60-kDa Ro autoantigen to Y RNAs: evidence for recognition in the major groove of a conserved helix. RNA. 1998 Jul;4(7):750-65.
- Pruijn GJ, Wingens PA, Peters SL, Thijssen JP, and van Venrooij WJ. Ro RNP associated Y RNAs are highly conserved among mammals. Biochim Biophys Acta. 1993 Dec 14;1216(3):395-401.
- van Gelder CW, Thijssen JP, Klaassen EC, Sturchler C, Krol A, van Venrooij WJ, and Pruijn GJ. Common structural features of the Ro RNP associated hY1 and hY5 RNAs. Nucleic Acids Res. 1994 Jul 11;22(13):2498-506.
File:BMCB625 Y RNA 061307.ppt
BMCB625:Noncoding Y RNA
Jeremy - Papers
- Zalfa F, Giorgi M, Primerano B, Moro A, Di Penta A, Reis S, Oostra B, and Bagni C. The fragile X syndrome protein FMRP associates with BC1 RNA and regulates the translation of specific mRNAs at synapses. Cell. 2003 Feb 7;112(3):317-27.
FMRP and BC1 RNA Slides
- Zalfa F, Achsel T, and Bagni C. mRNPs, polysomes or granules: FMRP in neuronal protein synthesis. Curr Opin Neurobiol. 2006 Jun;16(3):265-9. DOI:10.1016/j.conb.2006.05.010 |
- Bagni C and Greenough WT. From mRNP trafficking to spine dysmorphogenesis: the roots of fragile X syndrome. Nat Rev Neurosci. 2005 May;6(5):376-87. DOI:10.1038/nrn1667 |
- Klann E and Dever TE. Biochemical mechanisms for translational regulation in synaptic plasticity. Nat Rev Neurosci. 2004 Dec;5(12):931-42. DOI:10.1038/nrn1557 |
- Martignetti JA and Brosius J. BC200 RNA: a neural RNA polymerase III product encoded by a monomeric Alu element. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11563-7.
- Tiedge H, Chen W, and Brosius J. Primary structure, neural-specific expression, and dendritic location of human BC200 RNA. J Neurosci. 1993 Jun;13(6):2382-90.
- Bourne J and Harris KM. Do thin spines learn to be mushroom spines that remember?. Curr Opin Neurobiol. 2007 Jun;17(3):381-6. DOI:10.1016/j.conb.2007.04.009 |
- Darnell JC, Warren ST, and Darnell RB. The fragile X mental retardation protein, FMRP, recognizes G-quartets. Ment Retard Dev Disabil Res Rev. 2004;10(1):49-52. DOI:10.1002/mrdd.20008 |
Larry - Papers
- Ogi T and Lehmann AR. The Y-family DNA polymerase kappa (pol kappa) functions in mammalian nucleotide-excision repair. Nat Cell Biol. 2006 Jun;8(6):640-2. DOI:10.1038/ncb1417 |
News and Views
- Lehmann AR. New functions for Y family polymerases. Mol Cell. 2006 Nov 17;24(4):493-5. DOI:10.1016/j.molcel.2006.10.021 |
- Haracska L, Prakash L, and Prakash S. Role of human DNA polymerase kappa as an extender in translesion synthesis. Proc Natl Acad Sci U S A. 2002 Dec 10;99(25):16000-5. DOI:10.1073/pnas.252524999 |
- Einolf HJ and Guengerich FP. Kinetic analysis of nucleotide incorporation by mammalian DNA polymerase delta. J Biol Chem. 2000 May 26;275(21):16316-22. DOI:10.1074/jbc.M001291200 |
- Trincao J, Johnson RE, Escalante CR, Prakash S, Prakash L, and Aggarwal AK. Structure of the catalytic core of S. cerevisiae DNA polymerase eta: implications for translesion DNA synthesis. Mol Cell. 2001 Aug;8(2):417-26.
- Bebenek K and Kunkel TA. Functions of DNA polymerases. Adv Protein Chem. 2004;69:137-65. DOI:10.1016/S0065-3233(04)69005-X |
Pol Kappa Presentation
Jon - Papers
- Gao H, Cervantes RB, Mandell EK, Otero JH, and Lundblad V. RPA-like proteins mediate yeast telomere function. Nat Struct Mol Biol. 2007 Mar;14(3):208-14. DOI:10.1038/nsmb1205 |
Evidence that two smaller subunits of RPA bind weakly and preferentially to telomeric DNA. These telomere capping proteins have functional similarities (OB fold) with ssDNA binding proteins and may be involved in the recruitment of telomere maintenance proteins.
Jon - Bonus Materials
- Haring SJ and Wold MS. A common means to an end. Nat Struct Mol Biol. 2007 Mar;14(3):176-7. DOI:10.1038/nsmb0307-176 |
- Miller KM, Rog O, and Cooper JP. Semi-conservative DNA replication through telomeres requires Taz1. Nature. 2006 Apr 6;440(7085):824-8. DOI:10.1038/nature04638 |
- Suck D. Common fold, common function, common origin?. Nat Struct Biol. 1997 Mar;4(3):161-5.
- Eggleston A. Hush, hush: the origin of telomeric silence. Nat Cell Biol. 2000 Feb;2(2):E27. DOI:10.1038/35000097 |
cool RPA discussion
So many papers, so little time: Papers we would have liked to cover (note podcast link below)
- Olaussen KA, Dunant A, Fouret P, Brambilla E, André F, Haddad V, Taranchon E, Filipits M, Pirker R, Popper HH, Stahel R, Sabatier L, Pignon JP, Tursz T, Le Chevalier T, Soria JC, and IALT Bio Investigators.. DNA repair by ERCC1 in non-small-cell lung cancer and cisplatin-based adjuvant chemotherapy. N Engl J Med. 2006 Sep 7;355(10):983-91. DOI:10.1056/NEJMoa060570 |
- Kumagai A, Lee J, Yoo HY, and Dunphy WG. TopBP1 activates the ATR-ATRIP complex. Cell. 2006 Mar 10;124(5):943-55. DOI:10.1016/j.cell.2005.12.041 |
- Zegerman P and Diffley JF. Phosphorylation of Sld2 and Sld3 by cyclin-dependent kinases promotes DNA replication in budding yeast. Nature. 2007 Jan 18;445(7125):281-5. DOI:10.1038/nature05432 |
- Kitamura E, Blow JJ, and Tanaka TU. Live-cell imaging reveals replication of individual replicons in eukaryotic replication factories. Cell. 2006 Jun 30;125(7):1297-308. DOI:10.1016/j.cell.2006.04.041 |
Overlapping coverage but Podcast is interesting
- Zhou T, Xu L, Dey B, Hessell AJ, Van Ryk D, Xiang SH, Yang X, Zhang MY, Zwick MB, Arthos J, Burton DR, Dimitrov DS, Sodroski J, Wyatt R, Nabel GJ, and Kwong PD. Structural definition of a conserved neutralization epitope on HIV-1 gp120. Nature. 2007 Feb 15;445(7129):732-7. DOI:10.1038/nature05580 |
Nature podcast on Zhou paper