Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Research News and Views
  • Published:

Catalytic DNA: in training and seeking employment

Nature Biotechnology volume 17, pages 422–423 (1999)Cite this article

As far as anyone knows, DNA has been employed in the same occupation as the custodian of genetic information for about 3 billion years. DNA has solidly held this position in the inner workings of living systems for so many eons because it truly excels at its job. The special chemical makeup and structure of DNA allows cells to store vast amounts of information, in some cases for centuries, then faithfully pass along a copy of this information to the next individual in a long line of relatives. An understanding of the fundamental structure of DNA and of the processes by which DNA instructs enzymes to synthesize identical copies of itself has ushered in the golden age of molecular biology that endures to this day. Deservedly so, these classic characteristics of DNA have found their way into every life science textbook and have become entrenched in the minds of all of us who have studied biology.

So DNA can do chemistry, but can this biochemist-in-training learn the trade well enough to hold a position in the highly competitive field of biocatalysis? The obvious choice for DNA's first new job in three billion years is the targeted destruction of RNA. Deoxyribozymes, like antisense oligonucleotides, can be designed to bind any RNA molecule simply by following the rules of Watson–Crick base pairing. The successful fusion of the catalytic activities of deoxyribozymes with the target recognition capabilities of antisense oligonucleotides could produce deoxyribozymes whose utility might span the spectrum from basic biotechnology applications to advanced forms of therapeutics. To this end, Santoro and Joyce5 have created the RNA-cleaving "10–23" deoxyribozyme. This unique ribonuclease contains a catalytic core of only 15 nucleotides that is flanked on both sides by substrate-recognition domains. Although its size may indicate an enzyme that is rudimentary and unsophisticated, 10–23 is an extraordinary deoxyribozyme that can be engineered to cleave almost any RNA transcript simply by reorganizing the RNA-binding sequences6. Moreover, its catalytic efficiency of 109 m–1/min–1 in the presence of divalent magnesium is the best among all known DNA and RNA enzymes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Secondary-structure models and catalytic cores of several deoxyribozymes.

References

  1. Breaker, R.R. & Joyce, G.F. Chem. Biol. 1, 223–229 (1994).

    Article  CAS  Google Scholar 

  2. Sen, D. & Geyer, C.R. Curr. Opin. Chem. Biol. 2, 680–687 (1998).

    Article  CAS  Google Scholar 

  3. Gesteland, R.F., Cech, T.R. & Atkins, J.F. (eds). The RNA world. (Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY; 1999).

    Google Scholar 

  4. Breaker, R.R. Chem. Rev. 97, 371–390 (1997).

    Article  CAS  Google Scholar 

  5. Santoro, S.W. & Joyce, G.F. Proc. Natl. Acad. Sci. USA 94, 4262–4266 (1997).

    Article  CAS  Google Scholar 

  6. Santoro, S.W. & Joyce, G.F. Biochemistry 37, 13330–13342 (1998).

    Article  CAS  Google Scholar 

  7. Cairns, M.J. et al. Nat. Biotechnol. 17, 480– 486 (1999).

    Article  CAS  Google Scholar 

  8. Warashina, M. et al. Chem. Biol. 6, 237–250 (1999).

    Article  CAS  Google Scholar 

  9. Roth, A. & Breaker, R.R. Proc. Natl. Acad. Sci. USA 95, 6027–6031 (1998).

    Article  CAS  Google Scholar 

  10. Li, Y. & Breaker, R.R. Proc. Natl. Acad. Sci. USA 96, 2746–2751 (1999).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. assistant professor in the Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, KBT 452, 06520-8103 , CT

    Ronald R. Breaker

Authors
  1. Ronald R. Breaker
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Breaker, R. Catalytic DNA: in training and seeking employment. Nat Biotechnol 17, 422–423 (1999). https://doi.org/10.1038/8588

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/8588

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing