Transcript Slide 1
Isabel K. Darcy Mathematics Department Applied Mathematical and Computational Sciences (AMCS) University of Iowa http://www.math.uiowa.edu/~idarcy Hyeyoung Moon, Michigan Joint Rob Scharein, Hypnagogic Software with: Guanyu Wang, University of Iowa Danielle Washburn, University of Iowa This work was partially supported by the Joint DMS/NIGMS Initiative to Support Research in the Area of Mathematical Biology (NSF 0800285). ©2008 I.K. Darcy. All rights reserved Mathematical Model Protein = DNA = = = = C. Ernst, D. W. Sumners, A calculus for rational tangles: applications to DNA recombination, Math. Proc. Camb. Phil. Soc. 108 (1990), 489-515. protein = three dimensional ball protein-bound DNA = strings. Protein-DNA complex Heichman and Johnson Slide (modified) from Soojeong Kim Tangle = 3-dimensional ball containing strings where the endpoints of the strings are fixed on the boundary of the ball. = Protein = 3-dimensional ball DNA = strings ≠ Tangle = 3-dimensional ball containing strings where the endpoints of the strings are fixed on the boundary of the ball. = ≠ Protein = 3-dimensional ball DNA = strings For geometry: see 12-12:30 -Mary Therese Padberg, Exploring the conformations of protein-bound DNA: adding geometry to known topology, Wednesday, March 14, 12-12:30pm and poster . Topoisomerase II performing a crossing change on DNA: Cellular roles of DNA topoisomerases: a molecular perspective, James C. Wang, Nature Reviews Molecular Cell Biology 3, 430-440 (June 2002) Topoisomerases are involved in • Replication • Transcription • Unknotting, unlinking, supercoiling. • Targets of many anti-cancer drugs. Topoisomerases are proteins which cut one segment of DNA allowing a second DNA segment to pass through before resealing the break. • Crossing Change • Knot distance Let K1 and K 2 be knots. d(K1,K2 ) theminimumnumber of crossingchanges needed to convertK1 into K 2 where theminimum is takenover all diagrams of K1. • Unknotting number Let K be a knot. T henu ( K ) d ( K ,01 ) where is 01 theunknot. Example 01 31 Unknottingnumber of 31 u(31 ) 1 Figure: courtesy of Hyeyoung Moon • There are undetermined values in the knot distance table. • For example, 51 31 01 41 T hus, d (51 ,41 ) 3. 1 1 d (51 ,41 ) | (51 ) (41 ) | | 4 0 | 2. 2 2 Slide courtesy of Hyeyoung Moon Knot distance tabulation • The distances between two knots up to mirror images are tabulated. http://math.uiowa.edu/~idarcy/TAB/tabnov.pdf Slide courtesy of Hyeyoung Moon Knot distance tabulation T heknotdistanceshas been tabulated for rationalknots, some non - rationalknotsand compositeof rationalknots up to13 crossingusing thefollowingmathematic al theories[DS] : 1) Classification of distanceone rationalknots([DS1][T o]), 2) T riangleinequality, 1 3) d ( K1 , K 2 ) | ( K1 ) ( K 2 ) | 2 where ( K ) is thesignatureof K ([Mk]), Knot distance tabulation 4) Linkingform requirements on |H1(M k )| whereM k is thedouble strandedcoverof S 3 over K & H1(M k ) is thefirst homologygroup of that.([Mk]), 5) Homologyrequirements on H1(M k ) ([DS1]), 6) Unknottin g number one knotsare prime([Sc][Zh]). 7) [D, Moon] Jones polynomial Tangle Equations Determining upper bounds Determining upper bounds Rational Tangles Rational tangles alternate between vertical crossings & horizontal crossings. k horizontal crossings are right-handed if k > 0 k horizontal crossings are left-handed if k < 0 k vertical crossings are left-handed if k > 0 k vertical crossings are right-handed if k < 0 Note that if k > 0, then the slope of the overcrossing strand is negative, while if k < 0, then the slope of the overcrossing strand is positive. By convention, the rational tangle notation always ends with the number of horizontal crossings. Rational tangles can be classified with fractions. A knot/link is rational if it can be formed from a rational tangle via numerator closure. N(2/7) = N(2/1) Note 7 – 1 = 6 = 2(3) when B = c/d, E = f/g, and |cg – df| > 1 TopoICE in Rob Scharein’s KnotPlot.com Cover: Visual presentation of knot distance metric created using the software TopoICE-X within KnotPlot. A pair of knots in this graph is connected by an edge if they can be converted into one another via a single intersegmental passage. This graph shows all mathematically possible topoisomerase reaction pathways involving small crossing knots. D, Scharein, Stasiak. (Nucleic Acids Res., 2008; 36: 3515– 3521). All possible topoisomerase-mediated reaction pathways from the unknot to 5.1 involving rational knots with less than 14 crossings. Darcy I K et al. Nucl. Acids Res. 2008;36:3515-3521 © 2008 The Author(s) Tangle table is joint work with Rob Scharein, Danielle Washburn, Guanyu Wang, Melanie DeVries, et. al. A tangle which is not generalized Montisinos A tangle which is not generalized Montisinos A tangle which is not generalized Montisinos Table of 4-crossing parity zero 2-string tangles. D, Melanie DeVries, Danielle Washburn, Guanyu Wang, Rob Scharein, et al. Parity 0 Parity ∞ Parity 1 Table of 4-crossing parity infinity 2-string tangles. . Parity ∞ parity one 2-string tangles. Parity 1 Table of parity zero tangles 4 crossings: 6 tangles 5 crossings: 44 tangles 6 crossings: 228 tangles 7 crossings: 1430 tangles 8 crossings: 8868 tangles 9 crossings: 59878 tangles Note the table currently contains many repeats Crossing Sign Determination Right-hand Rule Right-handed Crossing +1 Left-handed Crossing -1 L positive crossing L negative crossing Signed crossing changes L L is called a crossingchange. L L is called a crossingchange. Signed knot distances d (K1,K2 ) is theminimum number of crossingchanges needed to convert K1 into K2 where only crossingchanges are allowed. d (K1,K2 ) is theminimumnumber of crossingchanges needed to convertK1 into K2 where only crossingchanges are allowed. Crossing Sign Determination Right-hand Rule Right-handed Crossing +1 Left-handed Crossing -1 TopoICE-R +1 tangle corresponds to a negative crossing since h + q + p(b+1) is odd Recombination: from the wall of the Pisa Cathedral. Photo courtesy of Rob Scharein Montesinos knot/link A Montesinosknot/linkis N( and a1 a r e) where e is an integraltangle b1 br ai is a rationaltanglefor i 1, ,r and r 3. Here, we assume ai and bi bi are relativelyprimeand 0 ai bi . T hatis, a1 ai is not an integraltangle. bi ar b1 e br Solving tangle equations Theorem [Hyeyoung Moon, D] For s,t 3, as 0 a1 N(U ) N( e1 ) 1 b1 bs zt x z1 and N(U ) N( e2 ) y v1 vt where ai ,bi ,e1 are integersand 0 ai bi for1 i s , x,y,zj ,v j ,e2 are integersand 0 z j v j for1 j t and U ( c c1 n ) (h1, ,hm ) is a generalized M - tangle. d1 dn Solving tangle equations if and onlyif for s,t 3 and for some 1 j1 s, (1) if m 1, thenU ( a j1 b j1 a j1 1 b j1 1 a j1 2 b j1 2 a j1 1 b j1 1 ) (e1 )and a j1 a j1 1 a j1 2 a j1 1 x zt z1 N( e2 ) N( e1 ) v1 vt b j1 b j1 1 b j1 2 b j1 1 y (2) if m 3 and hm 0, thenU ( where h1 e1 and N( N( a j1 b j1 a j1 1 b j1 1 a j1 b j1 a j1 1 b j1 1 z z1 t e2 ) v1 vt a j1 2 b j1 2 a j1 1 b j1 1 x e1 ). h2 x y a j1 2 b j1 2 a j1 1 b j1 1 ) (h1 , h2 ,0 ) Solving tangle equations (3) if m 3, hj 0 for all1 j m and hm 0 or if m 3, hj 0 for all a j m, then U ( a j1 b j1 a j1 1 b j1 1 a j1 3 b j1 3 a j1 2 b j1 2 ) (h1 , , hm ) E[hm , ,h3 ] a j1 1 zt z1 where h1 e1 and and N( e2 ) E[hm , ,h2 ] b j1 1 v1 vt N( a j1 b j1 a j1 1 b j1 1 a j1 3 b j1 3 a j1 2 b j1 2 xE[h3 , ,hm 1 ] yE[h3 , ,hm ] e1 ). xE[h2 , ,hm 1 ] yE[h2 , ,hm ] Note thatif h2 0 in (2), thesolutionis thesame as thesolutionin (1). Solving tangle equations Theorem [Hyeyoung Moon, D] For t 3, N(U z 0 a x z ) N( ) and N(U ) N( 1 t e2 ) 1 b y v1 vt where a,b,x,y,zj ,v j ,e2 are integersand 0 z j v j for1 j t and U is a generalized M - tangle. if and onlyif for t 3 , U ( c1 pa c1b pa c1b c1 ) (h,0 )and ( ) (h,0 ) for all integers d1 d1b qa d1b qa d1 c1 ,d1,p and q such thatd1 p-qc1 1 and 0 c1 d1 where h is an integer x z1 z 2 z3 c pa c1b x such that is not an integer.In thiscase, N( ) N( 1 ). hx y v1 v2 v3 d1 d1b qa hx y Note that thechoiceof c1 and p such thatd1 p-qc1 1 has no effecton U . Solving tangle equations Theorem 2.3 [Hyeyoung Moon, D] For s 3, N(U a 0 a x z ) N( 1 s e1 ) and N(U ) N( ) 1 b1 bs y v where ai ,bi ,e1 ,x,y,z,vare int egersand 0 ai bi for1 i s , and U is a generalized M - t angle. if and onlyif for s 3 , U ( c1 pz c1v x pz c1v c1 x ) (h,0 ) ( ) and ( ) (h,0 ) ( ) d1 d1v qz y d1v qz d1 y for all int egersc1 ,d1,p and q such t hatd1 p-qc1 1 where h is an int eger x is not an int egerfor y ' such t hat yy' 1 1 mod x. ' hx y a a a c pz c1v x In t hiscase, N( 1 2 3 e1 ) N( 1 ). b1 b2 b3 d1 d1v qz hx y ' such t hat Not e t hat t hechoiceof c1 and p such t hatd1 p-qc1 1 has no effecton U .