Processivity

Key takeaways

Processivity belongs to science; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Processivity to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Processivity from memory before moving on to harder problems.

Reference excerpt

In molecular biology and biochemistry, processivity is an enzyme's ability to catalyze "consecutive reactions without releasing its substrate". For example, processivity is the average number of nucleotides added by a polymerase enzyme, such as DNA polymerase, per association event with the template strand. Because the binding of the polymerase to the template is the rate-limiting step in DNA synthesis, the overall rate of DNA replication during S phase of the cell cycle is dependent on the processivity of the DNA polymerases performing the replication. DNA clamp proteins are integral components of the DNA replication machinery and serve to increase the processivity of their associated polymerases. Some polymerases add over 50,000 nucleotides to a growing DNA strand before dissociating from the template strand, giving a replication rate of up to 1,000 nucleotides per second.

DNA binding interactions Polymerases interact with the phosphate backbone and the minor groove of the DNA, so their interactions do not depend on the specific nucleotide sequence. The binding is largely mediated by electrostatic interactions between the DNA and the "thumb" and "palm" domains of the metaphorically hand-shaped DNA polymerase molecule. When the polymerase advances along the DNA sequence after adding a nucleotide, the interactions with the minor groove dissociate but those with the phosphate backbone remain more stable, allowing rapid re-binding to the minor groove at the next nucleotide. Interactions with the DNA are also facilitated by DNA clamp proteins, which are multimeric proteins that completely encircle the DNA, with which they associate at replication forks. Their central pore is sufficiently large to admit the DNA strands and some surrounding water molecules, which allows the clamp to slide along the DNA without dissociating from it and without loosening the protein–protein interactions that maintain the toroid shape. When associated with a DNA clamp, DNA polymerase is dramatically more processive; without the clamp most polymerases have a processivity of only about 100 nucleotides. The interactions between the polymerase and the clamp are more persistent than those between the polymerase and the DNA. Thus, when the polymerase dissociates from the DNA, it is still bound to the clamp and can rapidly reassociate with the DNA. An example of such a DNA clamp is PCNA (proliferating cell nuclear antigen) found in S. cervesiae.

Polymerase processivities Multiple DNA polymerases have specialized roles in the DNA replication process. In E. coli, which replicates its entire genome from a single replication fork, the polymerase DNA Pol III is the enzyme primarily responsible for DNA replication and forms a replication complex with extremely high processivity. The related DNA Pol I has exonuclease activity and serves to degrade the RNA primers used to initiate DNA synthesis. Pol I then synthesizes the short DNA fragments in place of the former RNA fragments. Thus Pol I is much less processive than Pol III because its primary function in DNA replication is to create many short DNA regions rather than a few very long regions. In eukaryotes, which have a much higher diversity of DNA polymerases, the low-processivity initiating enzyme is called Pol α, and the high-processivity extension enzymes are Pol δ and Pol ε. Both prokaryotes and eukaryotes must "trade" bound polymerases to make the transition from initiation to elongation. This process is called polymerase switching.

References

Further reading Watson JD, Baker TA, Bell SP, Gann A, Levine M, Losick R. (2004). Molecular Biology of the Gene 5th ed. Benjamin Cummings: Cold Spring Harbor Laboratory Press.

External links https://web.archive.org/web/20060517085321/http://opbs.okstate.edu/~melcher/mg/MGW4/Mg424.html Bedford, E; Tabor, S; Richardson, C. C. (1997). "The thioredoxin binding domain of bacteriophage T7 DNA polymerase confers processivity on Escherichia coli DNA polymerase I". Proceedings of the National Academy of Sciences of the United States of America. 94 (2): 479–484. Bibcode:1997PNAS...94..479B. doi:10.1073/pnas.94.2.479. PMC 19538. PMID 9012809. Tabor, S; Richardson, C. C. (1987). "DNA sequence analysis with a modified bacteriophage T7 DNA polymerase". Proceedings of the National Academy of Sciences of the United States of America. 84 (14): 4767–4771. Bibcode:1987PNAS...84.4767T. doi:10.1073/pnas.84.14.4767. PMC 305186. PMID 3474623.

Worked examples

Example 1 — a first encounter with Processivity

Start with the simplest possible case. Write down what Processivity claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In science, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Processivity before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Processivity ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Processivity

In research: Processivity appears in science research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Processivity in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Processivity is common in secondary-school and first-year university syllabi. It links to neighbouring topics DNA replication, Enzymes, so understanding it makes those chapters shorter.
In everyday life: Look for Processivity outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

How to study Processivity in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Processivity means in your own words.
Compare your version with the excerpt and mark what you missed.
Work through the three examples above with pen and paper.
Explain Processivity out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Processivity in simple terms?

In molecular biology and biochemistry, processivity is an enzyme's ability to catalyze "consecutive reactions without releasing its substrate". For example, processivity is the average number of nucleotides added by a polymerase enzyme, such as DNA polymerase, per association event with the templat…

Why does Processivity matter?

Because it connects several science ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Processivity?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Processivity.