TRF2 Lab Report

Instead of losing telomeres after each reproduction, the cells replenish, or lengthen, the telomeres using an enzyme called telomerase.

They have identified key molecules that regulate the cell cycle in all eukaryotic organisms, including yeasts, plants, animals and human. These fundamental discoveries have a great impact on all aspects of cell growth. Defects in cell cycle control may lead to the type of chromosome alterations seen in cancer cells. This may in the long-term open

Sufu has the ability to bind to GLI1, GLI2 and GLI3 proteins. It is theorized that GLI proteins are binded to Sufu in a head to tail orientation. GL1 is solely found in the nucleus, whereas Sufu can be found expressed in both the nucleus and the cytoplasm. However when they are both expressed together, Sufu brings the GLI1 into the cytoplasm which forces the nucleus to limit its transcription activity. The cytoplasm anchoring model suggests that GLI1 is anchored to the cytoplasm with the help of Sufu. Likewise, Sufu plays a similar role in Drosophilia by halting nuclear processes. Thus, it is found that Sufu travels back and forth between the cytoplasm and nucleus in both Drosophilia and mammals. A second model of Sufu function in mammals suggests the Sufu gene holds the ability of repressing transcription of GLIs. A study found that Sufu restricts GLI transcription by enlisting the help of the mSin3A HDAC corepressor complex. Sufu was also found to increase the ability of GLI1 to bind to DNA. Therefore, simply repressing the Sufu gene is enough to activate GLI transcription, alluding to its key role in the negative regulation of the SHH signaling

Telomerase (or terminal transferase) is an enzyme made of proteins, specifically reverse transcriptase (Telomerase Reverse Transcriptase-TERT), and RNA subunits. Nonetheless, chicken TERT (chTERT) shares 45% amino acid identity with human TERT (hTERT). However, chTERT is larger than the hTERT because of an extensive N-terminal flexible linker region. Also, chTERT is found on chromosome 2q21 near an interstitial telomere site. Generally, the role of this enzyme is to elongate the end of chromosomes by adding the repeated base sequence of TTAGGG, as described above. This enzyme can be found in fetal tissue, germ cells, and tumor cells. Telomerase activity is critical high on development because of the continued growth and division of the cells.

It has been suggested that abnormalities in the activity or expression of HDACs can lead to an imbalance of HDAC relative to histone acetyltransferase activity resulting in diminished expression of regulatory genes, which control the cell cycle and apoptosis developing tumorigenesis (Licciardi, Ververis, Hiong & Karagiannis, 2013). In some cases, HDAC enzymes are abnormally recruited to gene promoters, which constitutively repress gene expression causing cancer. In addition, HDACs alter gene expression due to the posttranslational deacetylation modification of various nonhistone protein substrates, such as DNA-binding proteins, DNA-repair proteins, transcription factors, signal-transduction molecules, and chaperone proteins(Licciardi, Ververis, Hiong & Karagiannis,

Then after DNA was extracted from a mouse live, and brain, the DNA decreased as it age ((DiMauro & David, 2009). DNA methylation is a procedure by which methyl gatherings are added to DNA. Once it is added, DNA’s function changes. Then if it is located in the promoter, the represses transcription, and transcription is important to constructing a gene expression. Early studies were on certain organs and life cycle of a humpback salmon. The studies on the salmon showed the 5-methylcytosine and otogenesis were decreasing. This shows the relationship between methylation and growth. Xist, H19,TARID are just a few noncoding RNA that affects methylation (Grammatikakis, Panda, Abdelmohsen, & Gorospe, 2014) . Xist is a RNA gene that is found on the X chromosome in mammals specifically females to level out the dosage effect in males. H19 is another lnRNA that limits body weight and cell production, but plays apart in the embryonic development and growth. Its controls imprinting and the loss of imprinting increases age related diseases. TARID prompts demethylation, and this helps trigger tumor suppressor

RACF is a conserved mechanism; such that RACF becomes pivotal for lamellipodia formation in mammalian cells and actin dynamics within the lamellipodia declines with age as seen in CD4 T-cells (Garcia et al., 2011). Our lab has established a model where RACF regulates lifespan by promoting inheritance of the fittest mitochondria into daughter cells. Since ykl∆ cells have extended lifespan, we tested whether ykl∆ cells may have altered rates of RACF.

The RNA-induced-silencing complex is used for gene regulation and in defense against viral and bacterial infections. The RISC is loaded with small dsRNAs that will guide the complex through base-pairing interactions to specific messenger RNA targets, which the RISC will help degrade. Once degraded, no more protein can be made from these mRNAs. The RNA-induced silencing complex can silence targeted genes through several mechanisms. It can work to repress translation during protein synthesis, interfere with the transcript level through mRNA degradation, or work at the level of the genome itself and eliminate DNA/form degrading materials. Heterochromatin is a degrading material that can be created to modify or suppress genes in the RISC (MacRae

TP53, also called tumor protein 53 is a tumor suppressor gene that encodes p53 and acts as a control center for the cell to act on when stressed (Brachova). Human p53 is a nuclear phsophoprotein of molecular weight 53kDa located on chromosome 17 containing 11 exons and 10 introns (Ling). One of its primary roles is as a transcription factor and in its active state is a homotetramer comprised of four 393 amino acid residues (Joerger , The tumor suppressor p53). Another main role p53 plays is as a tumor suppressor and once activated, protects against cancer by “functioning as a sequence-specific transcription factor, through protein-protein interactions, activating cell cycle arrest, apoptosis, and DNA damage repair (Brachova).”

This makes Nrf2 sense oxidative stress in the cells. Then, Nrf2 controls the tasks of the genes involved in the production and activation of vital detoxification molecules.

Out of these 31 exons, there are exons known as CREB domains that manage different TFs. Domains include: nuclear receptor interaction domain (NRID), transactivation zinc domains (TAZ1&2-cystein regions), CREB and MYB interaction domain (KIX), the bromo domain (bromo), histone acetyltransferase domain (HAT), and nuclear coactivator binding domain (NCBD), essentially in that order on the CREBBP gene sequence. Mutations can occur at any of these exons, but the most notable mutations occur at the HAT domain. This is due largely because when the protein is not acetylated the promoter site cannot be accessed by TFs [5]. This results in essential proteins for development not being produced, thus causing developmental anomalies. One such anomaly is the Rubenstein-Taybi syndrome (RTS), which is associated directly with CREBBP mutations [8]. Mutations in CREBBP are also associated with Huntington’s disease and acute myeloid leukemia, due to chromosomal

Hello Amy. I enjoyed reading your post. Individuals with telomere disorder have shorter telomeres for their age. One example of telomere disorder is Dyskeratosis congenita. This disorder caused by a mutation of TERT, TERC, DKC1 or TINF2 genes. Affected individuals have multiple medical problems affecting the nails, oral mucosa, and skin. They are also high risk of developing life-threatening conditions such as cancer and bone marrow failure. “Increasing telomerase levels ought to lengthen telomeres but in the case of cancer, too much telomerase can be just as bad as too little telomeres” (Rehman, 2014). Telomerase could slow down the aging process, but it could also increase the risk of developing cancer. Great job Michaela

As shown by the study when telomere function is not regulated they lose normal ability to regenerate which, thus far has been presumed as aging. Recent studies on neural stem cells have leading information on the mechanism of aging using p16INK4a overexpression and oppression in mice. The results indicated that an increase in p16INK4a contributes to a decrease in proliferation and function

Telomeres function as a means of protection for chromosomes. In DNA replication, the telomeres of a chromosome cannot be replicated, resulting in chromosomes becoming shortened over time (Vidak, 2016). This characteristic of telomeres gives great insight to the importance of functions of telomerase and telomeres on chromosomes, the impact telomeres have on aging, and the origin of RNA in telomerase. Telomere functionality and defects in regulation can also give great understanding to aging diseases in children such as Hutchinson-Gilford progeria syndrome (HGPS).

Cell cycle progression is orchestrated by a complex convergence of many signaling pathways. The decision to activate particular pathways while inhibiting others is mediated by a select group of gatekeeping proteins. At the molecular level, one particular interesting area of research is identifying particular proteins that function as crossroads of t