cancer

A detailed Summary of cancer

Few, if any, molecules can attest to being more important to life on earth than deoxyribonucleic acid (DNA). Life is based upon this critical molecule, as it defines the structure and function of each individual organism in which it is found. DNA comprises genes, which are responsible for the similarities between closely related organisms, as well as the unique and distinct differences that define individuals in these closely related groups. Such powerful and important responsibilities suggest that DNA must be greatly protected and preserved, and that changes in these critical DNA sequences could have devastating results. DNA sequences do, however, undergo changes and although the consequences of such changes in the genetic code can lead to disaster, there are mechanisms existing within the cell that may properly correct them. Such mechanisms are known collectively as DNA repair and they exist in several different forms (Setlow, 1998). Nucleotide excision repair (NER) is!

one such mechanism of preserving the DNA sequence and may be considered as not only the frontline of defense for a DNA molecule against sequence-damaging agents, but a possible defense mechanism against many forms of cancer as well.

In this case, UV light acts as an external factor that leads to not only DNA sequence damage, but, if the repair pathway has been inactivated by DNA sequence damage to a gene encoding one of its primary components, a dangerous and potentially deadly disease (Bonn, 1998). Complementation tests have identified seven different XP complementation groups, which relate to the specific repair genes XPA, XPB, XPC, XPD, XPE, XPF, and XPG (Wouter et al 2000).

The overview discussed in the opening paragraphs provides a very general description of the NER processes. However, in order to examine the two different methods of NER, it is perhaps most useful to utilize a specific example. In this case, a particularly effective choice is the nucleotide-excision repair pathway of individuals suffering from xeroderma pigmentosum (XP). XP is a rare cancer syndrome, which is caused by defects in this specific NER pathway. Individuals suffering from this disease are extremely sensitive to ultraviolet light. With a functional NER pathway, they would be able to repair DNA damage caused by UV light with relative ease. However, once this pathway is damaged these instances of UV light-induced DNA damage cannot be fixed (De Laat, 1998). In the case of XP, there is often a defect in a common component found in both GG-NER and TC-NER. The cause of this defect is usually a genetic mutation in a gene coding for a specific component of the pathw!

These are the main components of the nucleotide excision repair pathway. However, they may be used in differing ways between the two specific modes of this pathway. In GG-NER, all of the above-mentioned components are utilized. XPC-hHR23B is specific to this mechanism and is not found the TC-NER, which is the primary difference in the process by which these two modes act (Tamar, 1999). In GG-NER, hHR23B binds to XPC and stimulates its ability to act as a damage sensor and recruit the necessary components for repair. This stimulation is most likely a structural one as opposed to catalytic (De Laat et all, 1998). The complex can recognize damage on the surface of both single-stranded and double-stranded DNA, with a specific ability to recognize damage caused by UV light. Without this complex, GG-NER could not occur because the complex is solely responsible for signaling the rest of the DNA repair factors to begin work at a particular damage site. The ability of this com!

Additional experiments performed by Araujo and her colleagues provided evidence supporting the notion that the CAK subunits on TFIIH may inhibit NER activity (Araujo et al 2000). The NER reaction was followed in the presence of two different types of TFIIH complexes. One complex contained six subunits, while the other contained nine. The nine-subunit TFIIH contained CAK subunits and the six-subunit complex did not. When in the presence of an ATP-regenerating system, the CAK-containing TFIIH performed repair at a significantly slower rate than the TFIIH lacking the CAK. This suggests that CAK kinase may inhibit NER activity by phosphorylating some component of the reaction, specifically the carboxy-terminal domain of RNAPII (Araujo et al 2000). Additional experiments involving the CAK kinase inhibitor H-8 further supported the inhibitory activity of CAK. H-8 inhibits cdk7 from phosphorylating RNAPII and when it was added to the above reaction conditions some noticeable r!

If XPC-hHR23B is specific to the GG-NER pathway, then how is DNA damage detected in the TC-NER pathway? The answer appears to lie with RNA polymerase II, abbreviated as RNAPII. Molecules of RNAP II that are elongating may become blocked by the damaged regions in the transcribed strands, which may subsequently make them effective DNA damage-sensors. While most damage sites on transcribed strands rely on RNAPII to detect damage there are transcription bubbles created at some altered DNA sites that the XPC complex is able to bind with directly. Co

Some common words found in the essay are:
De Laat, XPG Wouter, DNA Life, GG-NER TC-NER, XPG ERCC1-XPF, XPG XPC-hHR23B, H-8 TFIIH, PCNA RF-C, XP XP, RNAP II, de laat, dna damage, laat et, et 1998, de laat et, laat et 1998, dna repair, dna sequences, nucleotide excision repair, dna sequence, al 2000, excision repair, et al 2000, nucleotide excision, araujo et al,

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Approximate Pages = 12 (250 words per page double spaced)

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