ScienceDaily (July 21, 2011) — For decades, scientists have known that DNA consists of four basic units -- adenine, guanine, thymine and cytosine. Those four bases have been taught in science textbooks and have formed the basis of the growing knowledge regarding how genes code for life. Yet in recent history, scientists have expanded that list from four to six.Speaking of textbooks, this amazing discovery couldn't have come at a better time since I'm just wrapping up the final chapters of my introductory biochemistry book. I'd better review what I wrote to see if I can include the 7th and 8th bases. Here's what I've got so far ...
Now, with a finding published online in the July 21, 2011, issue of the journal Science, researchers from the UNC School of Medicine have discovered the seventh and eighth bases of DNA.
These last two bases -- called 5-formylcytosine and 5 carboxylcytosine -- are actually versions of cytosine that have been modified by Tet proteins, molecular entities thought to play a role in DNA demethylation and stem cell reprogramming.
Much is known about the "fifth base," 5-methylcytosine, which arises when a chemical tag or methyl group is tacked onto a cytosine. This methylation is associated with gene silencing, as it causes the DNA's double helix to fold even tighter upon itself.
Last year, Zhang's group reported that Tet proteins can convert 5 methylC (the fifth base) to 5 hydroxymethylC (the sixth base) in the first of a four step reaction leading back to bare-boned cytosine.
DNA and RNA contain a number of modified nucleotides. The ones present in transfer RNA are well known (Section 21.8B) but the modified nucleotides in DNA are just as important. Some of the more common modified bases in DNA are shown in Figure 18.17. Most of them are only found in a few species or in bacteriophage while others are more widespread.Oh dear. Looks like I've made a serious mistake. I've shown bases #5, #6, #7, #8, #9, and #10 but everyone knows that up until yesterday only six bases were known.
We will encounter N6-methyladenine in the next chapter when we discuss restriction endonucleases. 5-Methylcytosine is a common modified base in mammalian DNA because it plays a role in chromatin assembly and the regulation of transcription. About 3% of all deoxycytidylate residues in mammalian DNA are modified to 5-methylcytidine.
Where did I go wrong? Can anyone help me out before I have to send this chapter to the printer?1
(The original Science paper is Ito et al. (2011). The authors really do imply that there are only six known modified nucleotides but they add an important qualifier that seems to have been played down the press release.)
1. One of my sources is Gomers-Apt and Borst (1995). In addition to the modified bases I've shown above they describe three forms of glycosylated hydroxymethyl cytosine (#11, #12, #13), uracil (#14), α-putrescinylthymine (#15), two different sugar substituted forms of 5-dihydroxypentyluracil (#16, #17), a-glutamylthymine (#18), 7-methylguanine (#19), N6-carbamoylmethyladenine (#20), N6-methylcytosine (#21), three versions of glycosylated 5-hydroxycytosine (#22, #23, #24) and β-D-hydroxymethyluracil (#25).
Gommers-Ampt, J.H. and Borst, A.P. (1995) Hypermodified bases in DNA. FASEB 9: 1034-1042 [FASEB]
Ito, S., Shen, L., Dai, Q., Wu, S.C., Collins, L.B., Swenberg, J.A., He, C., and Zhang, Y. (2011) Tet Proteins Can Convert 5-Methylcytosine to 5-Formylcytosine and 5-Carboxylcytosine. Science Published Online 21 July 2011 [doi:10.1126/science.1210597]