Candida
Dongyou Liu in Handbook of Foodborne Diseases, 2018
Many genes in Candida albicans potentially associated with meiosis were found, but this process under experimental conditions was not observed. This is a process resembling a parasexual cycle, wherein the loss of chromosomes is the last phase. Growth of Candida albicans tetraploid cell is associated with accidental loss of chromosomes, and the result is a diploid cell. The study of these diploid cells, formed during a parasexual cycle, confirm prior recombination of genetic material. It is considered that the parasexual cycle can change the abilities of yeast, opening new invasive opportunities. DNA recombination is the key to genetic diversity, and hence, an effective strategy to adapt to changing environmental conditions. This adaptation is expressed, for example, by the ability to change the phenotypic state of yeast, and some species form even seven different types of colonies. The ability to change the morphology is reversible and passed down from generation to generation.8
Science of biotechnology – Recombinant DNA technology
Ronald P. Evens in Biotechnology, 2020
The circular plasmid DNA must be cut open to accept the human DNA (gene) using unique bacterial enzymes (restriction endonucleases). Each endonuclease enzyme is highly specific to a certain nucleic acid sequence, creating a very specific cut, that is, an opening in the DNA plasmid structure appropriate for a specific gene’s incorporation and permitting efficient recombination. DNA materials will recombine naturally with the human gene sequence inserted into the circular plasmid sequence. A DNA ligase enzyme is employed to enhance the DNA recombination process. Figure 2.9 displays such restriction endonuclease enzymes found in nature in specific bacteria as noted. The very high specificity to an individual DNA sequence of nucleotides for endonucleases is shown in Figure 2.9.
Molecular Approaches Towards the Isolation of Pediatric Cancer Predisposition Genes
John T. Kemshead in Pediatric Tumors: Immunological and Molecular Markers, 2020
The principle of following disease phenotypes through families is known as “gene tracking” and requires that the location of the disease locus is known. The distance between two given genetic loci can be defined in two ways; actual physical distance and relative recombination distance. As its name implies, “physical distance” can be defined as the number of basepairs (bp), or thousands of basepairs — kilobases (kb)— between the two loci. The recombination distance is determined by the frequency with which genetic recombination occurs between given loci. In general, the farther the two loci are apart, the greater the chance of recombination. However, within the genome, there are some areas which show proportionately more recombination events and others which show fewer events than might be expected considering the physical distance between the two loci, a phenomenon illustrated by the long arm of the X chromosome.2 This concept is important when discussing gene tracking strategies since too frequent recombination between marker and disease loci makes prenatal prediction unreliable.
Emerging compounds and therapeutic strategies to treat infections from Trypanosoma brucei: an overhaul of the last 5-years patents
Published in Expert Opinion on Therapeutic Patents, 2023
Francesco Melfi, Simone Carradori, Cristina Campestre, Entela Haloci, Alessandra Ammazzalorso, Rossella Grande, Ilaria D’Agostino
Rhodesian (TbrCATL) belongs to the family of cathepsin L (CATL)-like proteases usually found in the parasite lysosomes and is important for survival, infectivity, and CNS penetration. It possesses a conserved catalytic triad (Cys/His/Asn) within its single chain of 215 peptidic residues [83], able to degrade both protozoan and host proteins, among which the variant surface glycoproteins (VSGs) of the parasite coat and protective immunoglobulins to escape the host immune system [84–86]. Antigenic variation in these VSGs is the main pathogenetic mechanism in T. brucei mediated by regular switching to maintain prolonged infections by bloodstream trypomastigotes [87]. Moreover, proteins involved in DNA recombination include RAD51, which mediates strand invasion in homologous recombination, RAD51-3, and BRCA2 that facilitate VSG switching, and proteins involved in DNA metabolism suppressing VSG switching. TRF and RAP1 are two telomere proteins with unique nucleic acid-binding activities, vital for T. brucei. In addition, TRF and RAP1 play crucial roles in antigenic variation; indeed, several telomere proteins have been identified in T. brucei. TbTRF is the duplex TTAGGG repeat binding factor and a TRF homolog; it associates with the telomere throughout the cell cycle, thus indicating the importance of TRF for the terminal telomere structure and cell proliferation [88]; defects in telomere integrity maintenance allow more VSG switching. TbRAP1 is a homolog of yeast and mammalian RAP1s.
Highly effective biosynthesis of N-acetylated human thymosin β4 (Tβ4) in Escherichia coli
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Rui Yu, Sai Cao, Yanhong Liu, Xinxi Si, Ting Fang, Xu Sun, Hongmei Dai, Junjie Xu, Hongqing Fang, Wei Chen
Escherichia coli (E. coli) is one of the widely used hosts in the field of genetic recombination. The most outstanding advantages of using this expression system include short production cycle, low cost, easy to scale up and high level of expression. However, there are two main obstacles of the biosynthesis of Tβ4 in E. coli: the bacterial expression of small peptides is difficult in general and this protein requires N-acetylation. Although there have been reports about the recombinant expression of human Tβ4 (rhTβ4), the expressions are relatively low (∼1 mg/L) and the sequences are not completely consistent with natural Tβ4 [29–31]. Some rhTβ4 are expressed by fusion with the label protein, and the extra amino acids are produced after cutting, some rhTβ4 are expressed in concatemer forms, and all of them are lack of N-acetylation. The non-natural sequence may affect the activity of Tβ4, and the lack of N-acetylation modification may seriously affect the stability of Tβ4. To this day, there is no report of N-acetylated rhTβ4 expressed in bacterial cells.
Investigational CHK1 inhibitors in early phase clinical trials for the treatment of cancer
Published in Expert Opinion on Investigational Drugs, 2019
In one phase II trial with LY2606368, with the drug as a single agent, is being tested in BRCA1/BRCA2 tumors including breast, ovarian and prostate. In another phase II trial, patients are recruited whose tumors exhibit replication stress or have homologous DNA recombination repair deficiencies. A phase I trial combining LY2606368 and the PARP1 inhibitor olaparib is also recruiting late-stage solid tumor patients [NCT03057145]. The majority of the listed trials are several years from reporting data, and based on prior experiences with CHK1 inhibitors, it remains to be seen whether LY2606368 will exhibit safety with a ‘signal’ for the compound to move toward phase II evaluation. Eli Lily also developed a second CHK1 inhibitor, LY2603618 (rabusertib) [36]. LY2603618 was clinically assed in seven trials [NCT00988858, NCT00415636, NCT01139775, NCT00839332, NCT01296568, NCT01358968, NCT01341457]. This agent underwent randomized phase II clinical testing in a variety of tumor types and was ultimately de-prioritized for its inability to enhance the efficacy of [pemetrexed + cisplatin] in non-small cell lung and head/neck cancers, or gemcitabine in pancreatic cancer.
Related Knowledge Centers
- Allele
- DNA
- DNA Repair
- Eukaryote
- Homologous Chromosome
- Meiosis
- Mitosis
- Genetics
- Parent
- Sequence Homology