DNA twisting flexibility and the formation of sharply looped protein-DNA complexes.
Gene-regulatory complexes often require that pairs of DNA-bound proteins interact by looping-out short (often approximately 100-bp) stretches of DNA. The loops can vary in detailed length and sequence and, thus, in total helical twist, which radically alters their geometry. How this variability is accommodated structurally is not known. Here we show that the inherent twistability of 89- to 105-bp DNA circles exceeds theoretical expectation by up to 400-fold. These results can be explained only by greatly enhanced DNA flexibility, not by permanent bends. They invalidate the use of classic theories of flexibility for understanding sharp DNA looping but support predictions of two recent theories. Our findings imply an active role for DNA flexibility in loop formation and suggest that variability in the detailed helical twist of regulatory loops is accommodated naturally by the inherent twistability of the DNA.
Cloutier
T E
TE
Department of Biochemistry, Molecular Biology, and Cell Biology, Northwestern University, Evanston, IL 60208-3500, USA.
Widom
J
J
D004247:DNA / Q000737:chemistry*; D005786:Gene Expression Regulation; D009690:Nucleic Acid Conformation; D011506:Proteins / Q000737:chemistry*
D011506:Proteins; D004247:DNA
J Mol Biol. 1987 Jul 5;196(1):101-11
3656441
Proc Natl Acad Sci U S A. 1988 Oct;85(19):7231-5
3174629
EMBO J. 1989 Nov;8(11):3491-9
2684643
J Mol Biol. 1990 Mar 20;212(2):351-62
2319603
J Mol Biol. 1990 Mar 20;212(2):363-76
2319604
Genes Dev. 1991 May;5(5):820-6
1851121
Cell. 1991 Aug 9;66(3):415-8
1868543
Annu Rev Biochem. 1992;61:199-223
1497310
Methods Enzymol. 1992;212:3-29
1518450
EMBO J. 1993 Feb;12(2):423-33
8440235
J Mol Biol. 1993 Mar 5;230(1):161-73
8450533
Nature. 1994 Mar 10;368(6467):163-6
8139661
EMBO J. 1995 Oct 2;14(19):4738-46
7588603
Nucleic Acids Res. 1995 Oct 11;23(19):3962-6
7479043
Trends Biochem Sci. 1995 Dec;20(12):500-6
8571451
Methods Enzymol. 1995;261:383-413
8569504
J Mol Biol. 1996 Mar 22;257(1):21-9
8632456
J Mol Biol. 1999 Oct 29;293(3):477-91
10543944
Nat Struct Biol. 2000 Mar;7(3):209-14
10700279
J Mol Biol. 2000 Jul 21;300(4):709-25
10891265
Proc Natl Acad Sci U S A. 2001 Jan 16;98(2):427-31
11209047
Q Rev Biophys. 2001 Aug;34(3):269-324
11838235
J Mol Biol. 2002 Mar 22;317(2):205-13
11902837
Biophys J. 2003 Jan;84(1):136-53
12524271
Nature. 2003 May 8;423(6936):145-50
12736678
Nature. 2003 Jul 17;424(6946):338-41
12867987
J Mol Biol. 2003 Aug 29;331(5):981-9
12927535
Mol Cell. 2004 May 7;14(3):355-62
15125838
Genes Dev. 2004 Aug 1;18(15):1898-907
15289461
Phys Rev Lett. 2004 Sep 3;93(10):108108
15447460
J Mol Biol. 2004 Oct 15;343(2):327-38
15451664
Nature. 1975 Jun 12;255(5509):530-3
1095931
Proc Natl Acad Sci U S A. 1981 Aug;78(8):4833-7
6272277
J Mol Biol. 1983 Nov 15;170(4):957-81
6315955
Nature. 1986 Jan 9-15;319(6049):121-6
3001535
Cell. 1986 Mar 14;44(5):681-7
3948245
J Mol Biol. 1996 Dec 20;264(5):919-32
9000621
Nature. 1997 Apr 10;386(6625):563
9121578
Science. 1998 Jul 3;281(5373):60-3
9679020
Proc Natl Acad Sci U S A. 1998 Sep 15;95(19):11163-8
9736707
Cell. 2005 Jan 14;120(1):37-48
15652480
Nature. 1988 Apr 28;332(6167):856-8
2833709
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2989-93
7708761
Annu Rev Biophys Biophys Chem. 1988;17:265-86
3293588
Proc Natl Acad Sci U S A. 1989 Jan;86(2):476-80
2643114