Ever heard of four-stranded DNA?

[Byung-Dong Kim]

Ever heard of four-stranded DNA?

It was during the 1982 Symposium on Structures of DNA. DNA molecule with many conformations was the main theme. The first session on June 2 was led by Alex Rich and other structural biologists. While listening to the presentations sitting among the packed audience in the Bush Lecture Hall my mind was running busy to figure out how to make sense out of the stem-and-loop structure of native mitochondrial DNA (mtDNA). The stem was not any thicker than double stranded region in the EM pictures that I have taken of the pearl millet mtDNA. Stem-and -loop structure of DNA being reminiscent of a transposable element stuck on my head for the past two years waiting for a good explanation.

It is highly unlikely, but by all means, if the stem-and-loop DNA were the real representation of a transposable element it would be very nice, because then the use of the terminal inverted repeats could be explained. Cruciform structure was the hot topic then to explain the utility of inverted repeats. Proteins such as DNA recombinase and transposase were known to mediate DNA recombination. I began to think that when inverted repeats can encounter their counterpart that close in the stem region, then complementarities between the two duplexes might be physically recognized.

How close do two duplexes have to be to recognize each other's complementary sequences? My eyes were fixed to the space filling model of B-DNA being displayed on the podium. There was one more such model brought by another crystallographer. I could not wait until coffee break when I walked to the front and asked for a permission of Tom Steitz to lay my hands on the models. I wanted to see if the two models could be brought together close enough to slide into each other's major groove and become of the same thickness as a double stranded DNA. Well, to my dismay, the major groove of standard B-DNA was not wide enough to let the other duplex slide in.

On Wednesday evening, dining hall of the Blackford Hall was sparsely occupied since speakers of the Symposium were invited to dine out by tradition at houses of the members of Long Island Biology Society. We were engaged in an idle after dinner talk. Scientists on my table were mostly from European countries. I was waiting my turn to talk. I changed the topic by asking "Has anyone ever heard of four-stranded DNA?" "Four-stranded DNA? No, I haven't." "No, I haven't either." My burning question about the possible existence of four-stranded DNA that had been lingering on my mind all the day fell flat. Someone on the next dinner table, however, overheard my questioning and came to our table. "Did you talk about four-stranded DNA?" "Yes, I did." "Why, are you interested in it?" "Yes, I am." "Well, I have published one article about a unique DNA structure in Science not long ago." Robert Hopkins and I walk out to the back yard lawn to get engaged into more serious talk about four-stranded DNA enjoying the evening breeze from the Cold Spring Harbor Bay.

I explained that I am preoccupied by the notion of four-stranded DNA based upon my EM pictures of some unusual shapes of mtDNA. Hopkins introduced me to his own Science paper and to Stewart McGavin's two papers in Journal of Theoretical Biology (1971 and 1977). For the first time I learned that there are a few people who talked about four-stranded DNA. This reinforced me that I am on the right track of thinking, but then I was anxious to know how much is already known about it by others. I hurried down to the library as I said good night to Hopkins. Library was still open. I was able to track down those references on four-stranded DNA. I decided to check as well the famous Watson and Crick's 1953 NATURE paper on double helical structure of DNA to find out for the first time that their paper was accompanied by two more papers, one by Morris Wilkins group and the other by Rosalind Franklin. CSHL was generous for visitors in making copies free of charge. I was able to copy a rather full collection of the earlier day references on DNA structure, which I had no easy access before. I was all set to take a journey into the wonderland of four-stranded DNA.

http://plaza.snu.ac.kr/~mglab/en_frame.htm