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Book of Abstracts: Albany 2007

category image Albany 2007
Conversation 15
June 19-23 2007

The ?Kink-and-Slide? folding of DNA in nucleosome is facilitated by asymmetric interactions of the histone arginines in the minor groove

Anisotropic bending of DNA in nucleosome is accompanied by lateral displacement of the adjacent base pairs, Slide, which is especially pronounced in those positions where DNA is sharply bent (or kinked) into the minor groove. The ?Kink-and-Slide? distortion is highly sequence-specific, being most favorable for the TA and CA:TG dimers, which is critical for the nucleosome positioning [1]. These deformations are generally consistent with the DNA conformational propensities, but the ?axial dislocations? observed in nucleosomal DNA are significantly amplified compared to the other protein-DNA complexes. To elucidate the mechanism(s) of this mutual-fit ?amplification? we analyzed the histone-DNA interactions in the two best-resolved nucleosome structures [2], paying special attention to the arginines in the minor groove.

The arginine guanidinium groups ?bridge? deoxyribose O4? atoms from the two DNA strands, somewhat similar to the hydration spine observed in the AT-rich DNA fragments. Unlike the water molecules, however, the arginines are positioned in the groove asymmetrically, being closer to one of the DNA strands. Importantly, the arginines penetrating into the minor groove at superhelical locations (-5.5, -4.5, -3.5, -2.5 and -0.5) are closer to the O4? atoms in the same DNA strand (namely, the strand whose 5?-to-3? direction goes from the location ?0.5 to location ?5.5). In the other half-nucleosome, the arginines are closer to the opposite DNA strand (with the 5?-to-3? direction going from 0.5 to 5.5).

We demonstrate how such an asymmetric positioning of arginines in the minor groove facilitates the ?unilateral? displacements of base pairs along their long axes, across the DNA grooves, thus leading to a stepwise accumulation of the superhelical pitch of the nucleosomal DNA [1]. The role of arginines in the DNA axial dislocations is best illustrated by the H2A arginines 42 and 77 penetrating into the minor groove at locations ±3.5 and ±5.5 respectively.

Finally, there is no perfect regularity in interactions of the histone arginines with the DNA minor groove ? the distances between the adjacent arginine positions vary from 9 to 12 bp. Importantly, these positions correlate remarkably well with the positions of the short ?A-tracts? in the nucleosomal DNA sequences from chicken and yeast [3,4]. (Here, only the 2-3 bp long ?A-tracts? are considered, containing the AA:TT and AT dimers, but no TA dimers.) Most likely, the structural ?reason? for such a correlation is that the narrow minor groove formed by the AT-rich sequences makes them most favorable for interactions with the positively charged arginines. We suggest using this ?irregular? AT-pattern to improve the predictive strength of the computer mapping of nucleosome positioning.

References and Footnotes
  1. Tolstorukov, M.Y., Colasanti, A.V., McCandlish, D., Olson, W.K. and Zhurkin, V.B. J Biomol Struct Dyn 22, 854-855, (2005).
  2. Davey, C.A., Sargent, D.F., Luger, K., Maeder, A.W. and Richmond, T.J. J Mol Biol 319, 1097-1113 (2002).
  3. Satchwell, S.C., Drew, H.R. and Travers, A.A. J Mol Biol 191, 659-675 (1986).
  4. Segal, E., Fondufe-Mittendorf, Y., Chen, L, Thastrom, A., Field, Y., Moore, I.K., Wang, J.P. and Widom, J. Nature 442, 772-778 (2006).

Difei Wang*
Feng Cui and
Victor B. Zhurkin

Laboratory of Cell Biology
National Cancer Institute, NIH
Bethesda, MD 20892, USA

*Phone: 301-451-7844
Fax: 301-402-4724
Email: wangdi@mail.nih.gov