Difference between revisions of "Part:BBa K076016"

Latest revision as of 12:17, 25 September 2024

Bleomycin

This gene is an antibiotic that allows for the selection of cells containing any construct that includes it.

Usage and Biology

CUHK-HongKong-SBS 2024

Bleomycin is classified within a subfamily of glycopeptide antibiotics, which includes vancomycin and is derived from the bacterium Streptomyces verticillus consisting of bleomycin A2 and B2 (1, 2) . Bleomycin A2 serves as the representative structure for Bleomycin. The subfamily is characterized by glycosylated peptide cores, which are thought to be integral to their mechanism of action in disrupting cellular processes. Bleomycin inhibits DNA synthesis and metabolism and is used as an antineoplastic, especially for solid tumors. The correlation between guanine and cytosine content and the degree of mitomycin-induced cross-linking is noteworthy. At elevated concentrations, bleomycin also suppresses cellular RNA and protein synthesis (2). The primary mechanism of action of bleomycin involves the ooxidative damage to DNA, facilitated by the formation of metallobleomycin complexes through binding with metal ions, including iron (3). The reactive oxygen species produced by these complexes lead to both DNA single-strand and double-strand breaks between 3'-4' bonds in deoxyribose. These strand breaks produce free base propenals particularly thymine, which are associated with cell cycle arrest at the G2 phase. This arrest inhibits cell replication, thereby preventing tissue growth and repair (4). Consequently, cytological examinations following bleomycin exposure reveal chromosomal aberrations, fragments, and chromatid breaks, along with detectable translocations.

References

1. Brandt, J. P., & Gerriets, V. (2020). Bleomycin. PubMed; StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK555895/

2. Drug Bank Online. (n.d.). Bleomycin. Go.drugbank.com. https://go.drugbank.com/drugs/DB00290

3. Petering, D. H., Byrnes, R. W., & Antholine, W. E. (1990). The role of redox-active metals in the mechanism of action of bleomycin. Chemico-Biological Interactions, 73(2-3), 133–182. https://doi.org/10.1016/0009-2797(90)90001-4

4. Murray, V., Chen, J. K., & Chung, L. H. (2018). The Interaction of the Metallo-Glycopeptide Anti-Tumour Drug Bleomycin with DNA. International Journal of Molecular Sciences, 19(5). https://doi.org/10.3390/ijms19051372

Sequence and Features