Model Building

[Byung-Dong Kim]

The first model I built was the canonical B-DNA. It was in Kingston, Rhode Island sometime in the fall of 1984. That year I attended the CSH Symposium on Recombination at the DNA Level. A twenty base pair column of double stranded DNA was built around a steel rod, which supported the structure as a helix axis. Two of the double helix models were built and brought close together. I tried to put them together tightly as I had done during the 1982 CSH Symposium with the CPK DNA models, but again, the major groove was rather too narrow to accept the other double helix in it. After brooding for some time I decided to remove the steel rod support. The B-DNA models lay flat on the floor. I realized that the DNA model was flexible even with the atomic torsion angles were fixed for B-DNA configuration. It was as if one can bend his elbow and wrist inwards but not outwards. I tried various manipulations on the model. As I twisted the double helix the major groove could be squeezed or widened to the extreme of parallel track beyond which point the model would break.
At this point I made two rather important discoveries, which had not been described previously as properties of double helix DNA. First, at the extreme unwinding of the helix two strands became parallel to each other as in an arch, but not straight on a flat surface, and the arch could be squeezed to form a small loop of DNA with as little as six base pairs. Second, both arms of the bent duplex DNA could slide into each other's major groove to form a four stranded DNA as unwinding of the double helix caused the major groove open wide enough to accept the other duplex DNA. The diameter was 2.2 nm for the four stranded DNA as well as for the double stranded DNA. This was the first realization that the B-DNA can foldback by bending 180o and squeeze into each other's major groove to form a four stranded DNA at the same thickness of double stranded DNA. This was the historical moment to confirm that the B-DNA molecule can assume the configurations consistent with my transmission electron microscope (TEM) pictures of the stem-and-loop structure and the stem structure of native mitochondrial DNA.

The next apparent step I undertook was to test with the space filling model whether the inverted repeats can undergo homologous recombination. Out of a 38 base pair-long duplex, I put 10 base pairs in the middle flanked by six base-pair inverted repeats so that they can make a direct physical contact in a stem-and-loop structure. In the four strand base pairing situation flipping of the inverted repeat bases 90o outwards placed them exactly in the position to pair by hydrogen bonding with the bases that were likewise flipped out of the complementary duplex, thus a heteroduplex in the inverted repeats was formed. This was in complete agreement with the prediction made by McGavin in 1971. When entangled sugar phosphate backbones were cut-pass-and-joined, presumably should be done by a recombinase, the synaptic complex was resolved. To my surprise, in the resulting molecule, the strand direction in the loop has been inverted, which is consistent with genetic and molecular biological reports. Homologous recombination between direct repeats in the loop configuration resulted in deletion of the internal sequence as a circular DNA molecule, which is again consistent with the literature. This was the historical moment to show that the DNA molecule itself is the major player of homologous recombination instead of a protein, recombinase that was supposed to bring those repeat sequences close by, cut, exchange sequences, and resolve. Utility of the repeat sequences as double stranded complementary base pairing partners in homologous recombination was realized.

My joy was doubled about this time as I cuddled around my first baby, Jihyun Jennifer, born in February of 1985 in Kingston, Rhode Island. We took lots of pictures of the baby in the background of yellow forthysias and pink rhododendrons in the backyard of the Heritage Drive 36. She was lovely and looked just after her mother, Il Young who was also a faculty at the University of Rhode Island.