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DNA and RNA exercises and their documents, Quizzes of Commercial Law

Istanbul Technical UniversityCommercial Law

DNA and RNA exercises and their documents

Typology: Quizzes

2017/2018

Uploaded on 06/17/2023

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MBG 208: Molecular Biology Assignment
Instructor
Sibel Sarı
The Assignment Title
DNA Repair and Diseases
The Assignment Date
16.05.2023
Submission Date
20.05.2023
Prepared by
2014011061
Hasan Batuhan KUCUK
ABDULLAH GUL UNIVERSTY
KAYSERI, 2023
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MBG 208: Molecular Biology Assignment Instructor Sibel Sarı The Assignment Title DNA Repair and Diseases The Assignment Date 16.05. Submission Date 20.05. Prepared by 2014011061 Hasan Batuhan KUCUK ABDULLAH GUL UNIVERSTY KAYSERI, 2023

The Table of Content

    1. The Nucleotide Excision Repair……………………………………......…….……….
    1. The Nucleotide Excision Repair and Xeroderma Pigmentosum……………...........…
    1. The Xeroderma Pigmentosum Group D........................................................................
    1. Mutations in the XPD Gene……………………………………….………..………....
    • 4.1. Cockayne Syndrome…………………………………………………………
      • A) Classical (moderate) Type 1 Cockayne Syndrome………………….……
      • B) Early- onset (severe) Subtypes……………………………………………
      • C) Late- onset Subtypes………………………………………………………
    • 4.2. Trichothiodystrophy………………………………………………………….
    • 4.3. Xeroderma pigmentosum (XP)……………………………………………….
    1. Reference List………………………………………………………………………….

early stage of life [3]. Premalignant lesions and skin cancers is notably higher and occurs significantly earlier in individuals than in those who lack such conditions [3]. Basal cell carcinomas, squamous cell carcinomas, and melanomas frequently emerge prior to reaching the age of 20, many years earlier than they typically occur in the general population [3]. Additionally, skin cancers associated with XP (xeroderma pigmentosum) often exhibit mutations caused by UV exposure, which strongly emphasizes the crucial role of NER (nucleotide excision repair) in protecting against cancer [3]. Figure 1 : The Nucleotide Excision Repair and eight enzymes and detecting DNA lesions [3]. The NER pathway states a coordinated collaboration among enzymes that work collectively to repair DNA lesions that modify the three-dimensional structure of the DNA [3]. Once the damage is identified and a repair complex comprising multiproteins is recruited to the affected site, the strand containing the damage is cut a few nucleotides away on both sides of the damaged bases [3]. The affected area is removed via excision and the subsequent void is replenished by a DNA polymerase that utilizes the non-compromised strand as a pattern [3]. Although only a small number of core factors are essential for repairing DNA lesions induced by UV radiation, there are numerous accessory factors that serve to regulate this pathway of genome maintenance [3]. THE XERODERMA PIGMENTOSUM GROUP D (XPD) The protein Xeroderma Pigmentosum Group D (XPD) is involved in two distinct processes, including nucleotide excision repair of DNA damage and basal transcription. [10]. The XPD gene which is located on chromosome 19q13.2, encodes a protein that spans 760 amino acids and is described by the presence of a helicase domain [13]. Figure 2 : The XPD gene [13]. The occurrence of loss-of-function mutations in the XPD gene within Xpd knockout mice

results in embryonic demise, underscoring the gene's indispensable role in development. [13]. If an individual carries two null alleles of the XPD gene, they will not survive [13]. Therefore, patients diagnosed with XPD must possess a missense mutation in the protein-coding gene, which alters its function while still allowing them to survive [13]. XPD is a multi-functional protein and constitutes a vital component of the transcription factor IIH (TFIIH) that is crucial in various cellular processes such as nucleotide excision repair (NER) for damaged DNA, transcription, and modulation of the cell cycle [13]. MUTATIONS IN THE XPD GENE Mutations in genes involved in nucleotide excision repair (NER), such as XPD, can give rise to a range of interconnected syndromes characterized by three broad categories of symptoms, besides increased sensitivity to sunlight (UV): Susceptibility to severe skin cancer as seen in xeroderma pigmentosum; Segmental progeria as observed in trichotiodystrophy and Cockayne syndrome; and their coexistence as seen in both XP/CS and XP/TTD [11]. Variations in the XPD helicase gene, which are necessary for the nucleotide excision repair (NER) process as an component of the transcription/repair complex TFIIH result in three distinct phenotypes [4]. These phenotypes include the cancer-susceptible disorder known as xeroderma pigmentosum (XP) as well as the two aging disorders Cockayne syndrome (CS) and trichothiodystrophy (TTD) [4]. Cockayne syndrome , an autosomal neurodegenerative condition, is caused by faulty DNA repair mechanisms that lead to poor neuronal growth, resulting in early aging and heightened vulnerability to sunlight [5]. In its initial observation in 1936, Cockayne syndrome was identified as a medical condition portraying concomitant features of dwarfism, retinal atrophy, and deafness [12]. It manifests as a broad range of symptoms that exhibit significant variations in their degree of severity [12]. The various indications associated with this condition comprise cutaneous photosensitivity, cataracts, dental anomalies, progressive neuronal degeneration, cognitive impairment, developmental deficiency, deep sunken eyes, and progeroid phenotype [12]. This syndrome can arise from mutations in several different genes, encompassing those responsible for encoding CSA, CSB, XPB, XPD, and XPG proteins [12]. Different degrees of severity have been identified in Cockayne syndrome, including the moderate type I or the "classical" form, the severe type II with early onset, and the mild type

the neurological and extraneurological symptoms characteristic of type I, typically after reaching the age of 10 years [9]. Trichothiodystrophy The medical condition known as Trichothiodystrophy (TTD) was initially characterized by Davies in 1968 as an infrequent autosomal syndrome that manifests in patients with sulfur- deprived frail hair, flaky dermis, and cognitive and physical disabilities [12]. In approximately half of all cases, patients also exhibit photosensitivity, yet without any notable correlation with skin cancer [12]. The occurrence of TTD can be attributed to mutations found in several genes that encode subunits belonging to the TFIIH, including the small 8 kDa subunit, XPB, and XPD [12]. Xeroderma pigmentosum (XP) Xeroderma pigmentosum (XP) is an infrequent, autosomal recessive disorder marked by a heightened susceptibility of the skin to sunlight [6]. Xeroderma Pigmentosum (XP) is recognized as one of the most well known afflictions associated with deficient Nucleotide Excision Repair (NER). The genetic mutations have been linked to ERCC1, XPA, XPB (ERCC3), XPC, XPD/ERCC2, DDB2/XPE, ERCC4/XPF, ERCC 5/XPG, and POLH/XPV. The signs of XP are primarily localized to the skin and eyes tissues. The degree of severity and penetrance of these symptoms are observed to be somewhat contingent upon the protein that is subjected to mutation, as well as the location of the mutation [2]. REFERENCES

  1. Bridges, B. A. (2001). SOS Repair. Encyclopedia of Genetics, 1853–1855. doi:10.1006/rwgn.2001.
  2. Cotterill, S. (2018). Diseases Associated with Mutation of Replication and Repair Proteins. Drosophila Models for Human Diseases, 215–234. doi:10.1007/978-981-13- 0529-0_
  3. D’Orazio, J., Jarrett, S., Amaro-Ortiz, A., & Scott, T. (2013). UV Radiation and the Skin. International Journal of Molecular Sciences, 14(6), 12222–12248. doi:10.3390/ijms
  1. Fan, L., Fuss, J. O., Cheng, Q. J., Arvai, A. S., Hammel, M., Roberts, V. A., … Tainer, J. A. (2008). XPD Helicase Structures and Activities: Insights into the Cancer and Aging Phenotypes from XPD Mutations. Cell, 133(5), 789–800. doi:10.1016/j.cell.2008.04.
  2. Gupta, R., Ambasta, R. K., & Kumar, P. (2020). Histone deacetylase in neuropathology. Advances in Clinical Chemistry. doi:10.1016/bs.acc.2020.09.
  3. Hanaoka, F. (2013). Xeroderma Pigmentosum. Brenner’s Encyclopedia of Genetics, 359–
    1. doi:10.1016/b978-0-12-374984-0.01654-
  4. Kovalchuk, I. (2016). Conserved and Divergent Features of DNA Repair. Genome Stability, 651–666. doi:10.1016/b978-0-12-803309-8.00038-
  5. Laugel, V. (2013). Cockayne syndrome: The expanding clinical and mutational spectrum. Mechanisms of Ageing and Development, 134(5-6), 161–170. doi:10.1016/j.mad.2013.02.
  6. Proietti-De-Santis, L., Laugel, V., & Prantera, G. (2019). Cockayne syndrome. Chromatin Signaling and Neurological Disorders, 135–152. doi:10.1016/b978-0-12-813796-3.00007- 9
  7. Taylor, E. M., Broughton, B. C., Botta, E., Stefanini, M., Sarasin, A., Jaspers, N. G. J., … Lehmann, A. R. (1997). Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene. Proceedings of the National Academy of Sciences, 94(16), 8658–8663. doi:10.1073/pnas.94.16.
  8. Van de Ven, M., Andressoo, J.-O., van der Horst, G. T. J., Hoeijmakers, J. H. J., & Mitchell, J. R. (2012). Effects of compound heterozygosity at the Xpd locus on cancer and ageing in mouse models. DNA Repair, 11(11), 874–883. doi:10.1016/j.dnarep.2012.08.
  9. Van Houten, B., & Kong, M. (2016). Eukaryotic Nucleotide Excision Repair. Encyclopedia of Cell Biology, 435–441. doi:10.1016/b978-0-12-394447-4.10045-
  10. Vashisht, A. A., & Wohlschlegel, J. A. (2019). Role of Human Xeroderma Pigmentosum Group D (XPD) Helicase in Various Cellular Pathways. Helicases from All Domains of Life, 125–139. doi:10.1016/b978-0-12-814685-9.00008-
  11. Van Zeeland, A. A., van Hoffen, A., & Mullenders, L. H. F. (2001). Nucleotide excision repair of UV-radiation induced photolesions in human cells. Sun Protection in Man, 377–
    1. doi:10.1016/s1568-461x(01)80054-