“Thymineless death”的意思、由来-开放百科全书

The phenomenon was first reported in 1954 by Hazel D. Barner and Seymour S. Cohen in Escherichia coli when thymine-requiring mutants of the bacteria lost viability when grown in a medium lacking thymine but containing other essential nutrients.^[4]^[5] Subsequently, this discovery led to the development of theories to explain the mechanism of action of several pyrimidine analogs that targeted thymine metabolism in bacteria and tumor cells.^[5]^[6] The phenomenon was commonly attributed to "unbalanced growth" wherein cells continued fundamental processes of RNA transcription, protein synthesis and metabolism in the absence of DNA replication.^[7] 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;^[1] DNA breaks were observed during thymineless death, which could explain the killing.^[8]^[9] Possible pathways involved with the killing mechanism include: replication initiation,^[8]^[10] breakage of ongoing replication forks,^[11] futile DNA repair,^[9] replication origin destruction,^[12] and an addiction module.^[13]

1. ^¹²{{cite journal|last=Ahmad|first=S. I.|author2=Kirk, S. H. |author3=Eisenstark, A. |title=Thymine Metabolism and Thymineless Death in Prokaryotes and Eukaryotes|journal=Annual Review of Microbiology|date=October 1998|volume=52|pages=591–625|doi= 10.1146/annurev.micro.52.1.591|pmid=9891809}}
2. ^{{Cite journal | last1 = Longley | first1 = D. B. | last2 = Harkin | first2 = D. P. | last3 = Johnston | first3 = P. G. | doi = 10.1038/nrc1074 | title = 5-Fluorouracil: Mechanisms of action and clinical strategies | journal = Nature Reviews Cancer | volume = 3 | issue = 5 | pages = 330–338 | year = 2003 | pmid = 12724731 | pmc = }}
3. ^{{Cite journal | last1 = Friedman | first1 = M. A. | last2 = Sadée | first2 = W. | title = The fluoropyrimidines: Biochemical mechanisms and design of clinical trials | journal = Cancer Chemotherapy and Pharmacology | volume = 1 | issue = 2 | pages = 77–82 | year = 1978 | pmid = 373913 | doi=10.1007/bf00254040}}
4. ^{{Cite journal | last1 = Barner | first1 = H. D. | last2 = Cohen | first2 = S. S. | title = The Induction of Thymine Synthesis by T2 Infection of a Thymine Requiring Mutant of Escherichia Coli | journal = Journal of Bacteriology | volume = 68 | issue = 1 | pages = 80–88 | year = 1954 | pmid = 13183905 | pmc = 357338}}
5. ^¹50 years ago in cell biology - A virologist recalls his work on cell growth inhibition
6. ^{{Cite journal | last1 = Cohen | first1 = S. S. | last2 = Flaks | first2 = J. G. | last3 = Barner | first3 = H. D. | last4 = Loeb | first4 = M. R. | last5 = Lichtenstein | first5 = J. | title = The Mode of Action of 5-Fluorouracil and Its Derivatives | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 44 | issue = 10 | pages = 1004–1012 | year = 1958 | pmid = 16590300 | pmc = 528686 | doi=10.1073/pnas.44.10.1004}}
7. ^{{Cite journal | last1 = Cohen | first1 = S. S. | last2 = Barner | first2 = H. D. | title = Studies on Unbalanced Growth in Escherichia Coli | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 40 | issue = 10 | pages = 885–893 | year = 1954 | pmid = 16589586 | pmc = 534191 | doi=10.1073/pnas.40.10.885}}
8. ^¹{{Cite journal | last1 = Martín | first1 = C. M. | last2 = Guzmán | first2 = E. C. | doi = 10.1016/j.dnarep.2010.10.005 | title = DNA replication initiation as a key element in thymineless death | journal = DNA Repair | volume = 10 | issue = 1 | pages = 94–101 | year = 2011 | pmid = 21074501 | pmc = }}
9. ^¹{{Cite journal | last1 = Nakayama | first1 = K. | last2 = Kusano | first2 = K. | last3 = Irino | first3 = N. | last4 = Nakayama | first4 = H. | title = Thymine starvation-induced structural changes in Escherichia coli DNA. Detection by pulsed field gel electrophoresis and evidence for involvement of homologous recombination | journal = Journal of Molecular Biology | volume = 243 | issue = 4 | pages = 611–620 | year = 1994 | pmid = 7966286 | doi=10.1016/0022-2836(94)90036-1}}
10. ^{{Cite journal | last1 = Sangurdekar | first1 = D. P. | last2 = Hamann | first2 = B. L. | last3 = Smirnov | first3 = D. | last4 = Srienc | first4 = F. | last5 = Hanawalt | first5 = P. C. | last6 = Khodursky | first6 = A. B. | doi = 10.1111/j.1365-2958.2010.07072.x | title = Thymineless death is associated with loss of essential genetic information from the replication origin | journal = Molecular Microbiology | volume = 75 | issue = 6 | pages = 1455–1467 | year = 2010 | pmid = 20132444 | pmc = }}
11. ^{{Cite journal | last1 = Kuong | first1 = K. J. | last2 = Kuzminov | first2 = A. | doi = 10.1111/j.1365-2443.2010.01405.x | title = Stalled replication fork repair and misrepair during thymineless death in Escherichia coli | journal = Genes to Cells | volume = 15 | issue = 6 | pages = 619–634 | year = 2010 | pmid = 20465561 | pmc = 3965187}}
12. ^{{Cite journal | pmid = 22621921| pmc = 3390671| year = 2012| author1 = Kuong| first1 = K. J.| title = Disintegration of nascent replication bubbles during thymine starvation triggers RecA- and RecBCD-dependent replication origin destruction| journal = The Journal of Biological Chemistry| volume = 287| issue = 28| pages = 23958–70| last2 = Kuzminov| first2 = A| doi = 10.1074/jbc.M112.359687}}
13. ^{{Cite journal | last1 = Sat | first1 = B. | last2 = Reches | first2 = M. | last3 = Engelberg-Kulka | first3 = H. | title = The Escherichia coli mazEF Suicide Module Mediates Thymineless Death | journal = Journal of Bacteriology | volume = 185 | issue = 6 | pages = 1803–1807 | year = 2003 | pmid = 12618443 | pmc = 150121 | doi=10.1128/jb.185.6.1803-1807.2003}}

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