MATH:7450 (22M:305) Topics in Topology: Scientific and Engineering Applications of Algebraic - PowerPoint Presentation

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MATH:7450 (22M:305) Topics in Topology: Scientific and Engineering Applications of Algebraic Topology

Nov 13, 2013: DNA Topology II

Fall 2013 course offered through the

University of Iowa Division of Continuing Education

Isabel K. Darcy, Department of Mathematics

Applied Mathematical and Computational Sciences, University of Iowa

http://www.math.uiowa.edu/~idarcy/

AppliedTopology.htmlSlide2

Biologically relevant topological structures of DNA. Depicted are schematics of the three topological forms of DNA that topoisomerases maintain and modulate.

Liu Z et al. Nucl. Acids Res. 2009;37:661-671

© 2009 The Author(s)‏Slide3
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http://www.personal.psu.edu/rch8/workmg/Struc_Nucleic_Acids_Chpt2.htmSlide5

http://www.personal.psu.edu/rch8/workmg/Struc_Nucleic_Acids_Chpt2.htmSlide6

DNA substrate = starting conformation of DNA before protein action

Usually unkotted, andsupercoiledMeiotic double-strand breaks in yeast artificial chromosomes containing human DNAGrzegorz Ira,  Ekaterina Svetlova, Jan FilipskiNucl. Acids Res. (1998) 26 (10):2415-2419http://www.personal.psu.edu/rch8/workmg/Struc_Nucleic_Acids_Chpt2.htmSlide7

Structure of the nucleosome.

Barbi M et al. Interface Focus 2012;2:546-554

©2012 by The Royal SocietySlide8

One of the many possible models of chromatin fibre, in a more condensed (a) and a less condensed (b) configuration.

Barbi M et al. Interface Focus 2012;2:546-554

©2012 by The Royal SocietySlide9

www.biophysics.org

/Portals/1/PDFs/Education/Vologodskii.pdfNicked circular DNASlide10

www.biophysics.org

/Portals/1/PDFs/Education/Vologodskii.pdfsupercoiled DNASlide11

http://www.ch.cam.ac.uk/magnus/molecules/nucleic/dna1.jpg

http://www.accessexcellence.org/RC/VL/GG/images/dna_replicating.gifSlide12

(J. Mann) http://

www.sbs.utexas.edu/herrin/bio344/

Postow L. et.al. PNAS;2001;98:8219-8226Slide13

Cellular roles of DNA topoisomerases: a molecular perspective

, James C. Wang, Nature Reviews Molecular Cell Biology 3, 430-440 (June 2002)Topoisomerase II performing a crossing change on DNA:Slide14

Proposed mechanisms for type I topoisomerases.

Dekker N H et al. PNAS 2002;99:12126-12131

©2002 by National Academy of SciencesSlide15

Topoisomerases are involved in

Replication Transcription Unknotting, unlinking, supercoiling. Targets of many anti-cancer drugs.Slide16

Type II topoisomerases are proteins which cut one segment of DNA allowing a second DNA segment to pass through before resealing the break.Slide17

http://

knotplot.com/zooSlide18

Duplex DNA knots produced by Escherichia coli topoisomerase I.

Dean FB, Stasiak A, Koller T, Cozzarelli NR., J Biol Chem. 1985 Apr 25;260(8):4975-83. Slide19
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http:

//www.sciencemag.org/content/277/5326/690.full.pdf, Science. 1997;277(5326):690-3.Slide21

What products would you predict if topoisomerase acted exactly once on the following 5 crossing knot?Slide22

.

..Slide23

.

..Lynn Zechiedrich and Jennifer Mann, unpublished result.Slide24
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How can topoisomerase

acting locally determine best action for global result, unknotting the DNA??Slide26

Model of type II topoisomerase action.

Vologodskii A V et al. PNAS 2001;98:3045-3049

©2001 by National Academy of SciencesSlide27

J

Mol Biol. 2004 Jul 23;340(5):933-9.DNA disentangling by type-2 topoisomerases.Buck GR, Zechiedrich EL.Slide28

The hooked juxtaposition hypothesis.

Liu Z et al. Nucl. Acids Res. 2009;37:661-671

© 2009 The Author(s)‏Slide29

The juxtaposition-centric computational approach.

Liu Z et al. Nucl. Acids Res. 2009;37:661-671

© 2009 The Author(s)‏Slide30
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Recombination: