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J. Arsuaga- DNA Supercoiling

Apr 06, 2018

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    March 16, 2010Math 414-1 / 714-1 Lecture 13

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    3.2 DNA in nature is found in circular form

    (plasmids) or as structures topologicallyequivalent to circles

    Bates and Maxwel, DNA topology, 2005

    Oxford University Press

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    3.3. Supercoiling naturally appears in

    many biological processes such as DNAreplication

    Bates and Maxwel, DNA topology, 2005

    Oxford University Press

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    Supercoiling is observed in

    chromosomes and is essential for cellviability

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    Biological roles of supercoiling

    DNA compaction

    Helps the opening of the double helix during

    DNA replication and transcription

    Site-specific recombination

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    Supercoiling is a wellness sensor for the

    cell

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    Supercoiling has broad implications in

    replication & transcription

    Replicated

    domain

    Replicating

    domain

    Pre-

    replicated

    domain

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    Who takes care of Supercoiling in the

    cell? Enzymes; type I andtype II topoisomerases

    Figure courtesy of J. Roca

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    Supercoiling in agarose gels

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    3.4 How can we quantify supercoiling?

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    How can we quantify supercoiling?

    Intuitively: Supercoiling happens due to anexcess of the number of times that the two

    DNA backbones coil around each other.

    Note to the students: the following slides

    are vague and should be complemented

    with your lecture notes

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    Consider a linear fragment of DNA:N=Number of base-pairs of thefragment

    h=Number of base pairs/helical turnLk0=N/h~ #helical turn

    Consider a planar circular molecule :Lkm= Closest integer to N/h

    J. Arsuaga, math 195-3

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    How can we compute the linking number

    of any DNA molecule?General definition of Linking Number

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    +1

    +1

    +1

    -1

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    +1

    +1

    +1

    -1

    Lk=1/2( sign(ci))

    c1

    c2

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    Supercoiling

    Linking number difference:Lk=Lk- Lk

    0

    Why Lk0 instead of Lkm?

    J. Arsuaga, math 195-3

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    Supercoiling density: = Lk/ Lk0

    Example:

    In E. coli = -0.06

    J. Arsuaga, math 195-3

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    Geometrical parameters Twist: Measures the coiling of the two

    individual strands.

    Tw0=N/h for open circular notnecessarily planar due to intrinsic curvature.

    Writhe: Describes how the helix axis coilsin space.

    Wr0=due to intrinsic curvature

    J. Arsuaga, math 195-3

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    Calugareanu-White-Fuller Theorem

    Lk=Tw+Wr

    J. Arsuaga, math 195-3

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    Computer simulations of DNA

    supercoiling: MD and Monte-Carlo

    [Jian et al., 1998; Huang et al., 2001]

    J. Arsuaga, math 195-3

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    Supercoiling is a wellness sensor for the

    cell

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    Chapter IV: The mathematics of DNA

    supercoiling

    Experimental evidence forsupercoiling and basicdefinitions.

    Linking number, twist andwrithe

    Whites theorem Modern experimental

    techniques to studysupercoiling andapplications

    J. Arsuaga, math 195-3