Thymineless death is the phenomenon by which bacteria, yeasts and mammalian cells undergo

cell death Cell death is the event of a biological cell ceasing to carry out its functions. This may be the result of the natural process of old cells dying and being replaced by new ones, as in programmed cell death, or may result from factors such as di ...

when they are starved of

thymidine triphosphate Thymidine triphosphate (TTP), also called deoxythymidine triphosphate (dTTP), is one of the four nucleoside triphosphates that are used in the ''in vivo'' synthesis of DNA. Unlike the other deoxyribonucleoside triphosphates, thymidine triphosphate ...

(dTTP), an essential precursor for

DNA replication In molecular biology, DNA replication is the biological process of producing two identical replicas of DNA from one original DNA molecule. DNA replication occurs in all life, living organisms, acting as the most essential part of heredity, biolog ...

. This phenomenon underlies the mechanism of action of several

antibacterial An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...

antimalarial Antimalarial medications or simply antimalarials are a type of antiparasitic chemical agent, often naturally derived, that can be used to treat or to prevent malaria, in the latter case, most often aiming at two susceptible target groups, young ...

and

anticancer An anticarcinogen (also known as a carcinopreventive agent) is a substance that counteracts the effects of a carcinogen or inhibits the development of cancer. Anticarcinogens are different from anticarcinoma agents (also known as anticancer or ant ...

agents, such as

trimethoprim Trimethoprim (TMP) is an antibiotic used mainly in the treatment of bladder infections. Other uses include for middle ear infections and travelers' diarrhea. With sulfamethoxazole or dapsone it may be used for ''Pneumocystis'' pneumonia ...

sulfamethoxazole Sulfamethoxazole (SMZ or SMX) is an antibiotic. It is used for bacterial infections such as urinary tract infections, bronchitis, and prostatitis and is effective against both gram negative and positive bacteria such as ''Escherichia coli' ...

methotrexate Methotrexate, formerly known as amethopterin, is a chemotherapy agent and immunosuppressive drug, immune-system suppressant. It is used to treat cancer, autoimmune diseases, and ectopic pregnancy, ectopic pregnancies. Types of cancers it is u ...

and

fluorouracil Fluorouracil (5-FU, 5-fluorouracil), sold under the brand name Adrucil among others, is a cytotoxic chemotherapy medication used to treat cancer. By intravenous injection it is used for treatment of colorectal cancer, oesophageal cancer, stoma ...

History

The phenomenon was first reported in 1954 by Hazel D. Barner and Seymour S. Cohen in ''

Escherichia coli ''Escherichia coli'' ( )Wells, J. C. (2000) Longman Pronunciation Dictionary. Harlow ngland Pearson Education Ltd. is a gram-negative, facultative anaerobic, rod-shaped, coliform bacterium of the genus '' Escherichia'' that is commonly fo ...

'' when thymine-requiring mutants of the bacteria lost viability when grown in a medium lacking

thymine Thymine () (symbol T or Thy) is one of the four nucleotide bases in the nucleic acid of DNA that are represented by the letters G–C–A–T. The others are adenine, guanine, and cytosine. Thymine is also known as 5-methyluracil, a pyrimidine ...

but containing other essential nutrients.50 years ago in cell biology - A virologist recalls his work on cell growth inhibition
/ref> Subsequently, this discovery led to the development of theories to explain the mechanism of action of several

pyrimidine Pyrimidine (; ) is an aromatic, heterocyclic, organic compound similar to pyridine (). One of the three diazines (six-membered heterocyclics with two nitrogen atoms in the ring), it has nitrogen atoms at positions 1 and 3 in the ring. The oth ...

analogs that targeted thymine metabolism in bacteria and tumor cells. The phenomenon was commonly attributed to "unbalanced growth" wherein cells continued fundamental processes of

RNA transcription Transcription is the process of copying a segment of DNA into RNA for the purpose of gene expression. Some segments of DNA are transcribed into RNA molecules that can encode proteins, called messenger RNA (mRNA). Other segments of DNA are transc ...

protein synthesis Protein biosynthesis, or protein synthesis, is a core biological process, occurring inside cells, balancing the loss of cellular proteins (via degradation or export) through the production of new proteins. Proteins perform a number of critica ...

and

metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...

in the absence of DNA replication. However, nutrient starvation does not generally kill cells to the extent observed in cells that lack thymine. The molecular mechanism of thymineless death remains unknown; DNA breaks were observed during thymineless death, which could explain the killing. Possible pathways involved with the killing mechanism include: replication initiation, breakage of ongoing replication forks, futile DNA repair, replication origin destruction, and an addiction module.

References

External links

{{Death Antibiotics