Microbiology and Immunology

Operon WORLD OF MICROBIOLOGY AND IMMUNOLOGY

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be seen if a mutation is present. All of the newer techniques

are more sensitive than cytogenetic analysis and can pick up

abnormal cell lines occurring at very low frequencies.

Clinically, it may be useful to detect the disease in an early

stage when there are fewer cancer cells present so that treat-

ment may begin before severe symptoms are experienced. In

addition, these techniques aid in detection of minimal residual

disease (the presence of low levels of disease after treatment)

and may give warning that the disease is returning.

A major breakthrough has come in treatment of dis-

eases caused by oncogenes. The current standard of care for

cancer patients has been chemotherapyand radiation therapy.

This is successful in limiting or eradicating the disease, but,

because the whole body is affected by these treatments, there

are usually multiple side effects such as hair loss, nausea,

fatigue, etc. New drugs are designed to counteract the partic-

ular mutation associated with the patient’s disease and thus

are target specific. This is only possible if the mutation caus-

ing the disease is known and a treatment can be developed

that inactivates the negative affect of that mutation. Because

only one cellular component is affected, negative physical

side effects may be reduced.

The most successful of these drugs to date is STI-571,

or Gleevec, and was developed for use in patients with chronic

myelogenous leukemia (CML). In CML, the proto-oncogene

translocation results in overproduction of the enzyme tyrosine

kinase. Gleevec is an inhibitor of tyrosine kinase and works at

the cellular level to block excess enzyme activity. Although

there are several different types of tyrosine kinase in humans,

STI-571 is specific to the form produced by the CML mutation

and does not affect other members of this enzyme family. The

drug is therefore so specific, other cells and tissues in the body

are not impacted, and there are few negative side effects

resulting in a therapy that is much more tolerable to the

patient. Early clinical trials showed such a high degree of suc-

cess that the trails were terminated early and the drug was

FDA approved and released for general use. There is now new

evidence to suggest that this drug also may be effective for

other diseases, including some types of solid tumors. This is

clearly the way drug treatments will be designed in the future.

By targeting only the defect and correcting that, a disease can

be managed without impairing other aspects of a patient’s

health or quality of life.

Other types of ongoing research include further elucida-

tion of normal proto-oncogene function and how the onco-

genic mutations change cellular regulation. In particular,

issues involving oncogeneimpact on apoptosis, programmed

cell death, have become an important avenue of investigation.

It has been shown that normal cells have a fixed life span but

that cancer cells lose this characteristic and exhibit uncon-

trolled cell growth with aspects of immortality. A better under-

standing of the role oncogenes play in this process may give

insight into additional ways to treat cancer.

See also Fluorescence in situ hybridization (FISH);

Immunogenetics; Immunologic therapies; Mutations and

mutagenesis

OOperonPERON

An operon is a single unit of physically adjacent genes that

function together under the control of a single operator gene.

With respect to transcriptionand translation, the genes within

an operon code for enzymesor proteins that are functionally

related and are usually members of a single enzyme system.

The operon is under the control of a single gene that is

responsible for switching the entire operon “on” or “off.” A

repressor molecule that is capable of binding to the operator

gene and switching it, and consequently the whole operon,

off, controls the operator gene. A gene that is not part of the

operon produces the repressor molecule. The repressor mole-

cule is itself produced by a regulator gene. The repressor

molecule is inactivated by a metabolite or signal substance

(effector). In other words, the effector causes the operon to

become active.

The lacoperon in the bacterium E. coliwas one of the

first discovered and still remains one of the most studied and

well known. The deoxyribonucleic acid(DNA) segment con-

taining the lacoperon is some 6,000 base pairs long. This

length includes the operator gene and three structural genes

(lacZ, lacY, and lacA). The three structural genes and the

operator are transcribed into a single piece of messenger

ribonucleic acid (mRNA), which can then be translated.

Transcription will not take place if a repressor protein is bound

to the operator. The repressor protein is encoded by lacI,

which is a gene located to the left of the lacpromoter. The lac

promoter is located immediately to the left of the lacoperator

gene and is outside the lacoperon. The enzymes produced by

this operon are responsible for the hydrolysis (a reaction that

adds a water molecule to a reactant and splits the reactant into

two molecules) of lactose into glucose and galactose. Once

glucose and galactose have been produced, a side reaction

occurs forming a compound called allolactose. Allolactose is

the chemical responsible for switching on the lacoperon by

binding to the repressor and inactivating it.

Operons are generally encountered in lower organisms

such as bacteria. They are commonly encountered for certain

systems, suggesting that there is a strong evolutionary pres-

sure for the genes to remain together as a unit. Operons have

not yet been found in higher organisms, such as multicellular

life forms.

A mutation in the operator gene that renders it non-func-

tional would also render the whole operon inactive. As a direct

result of inactivation, the coded pathway would no longer

operate within the cell. Even though the genes are still sepa-

rate individual units, they cannot function by themselves,

without the control of the operator gene.

See alsoGenetic code; Microbial genetics

OOpsonizationPSONIZATION

Opsonization is a term that refers to an immune process where

particles such as bacteriaare targeted for destruction by an

immune cell known as a phagocyte. The process of opsoniza-

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