DNA repair and transcription deficiency syndromes
The genetic information of all living organisms is stored in DNA, a long macromolecule composed of four different nucleotides. Preservation of the sequence of nucleotides, defining the genetic code, is a prerequisite for a faithful transmission of the genetic information to subsequent generations and for accurate expression of this coded information. Although DNA is a relatively stable molecule, it is vulnerable to changes by metabolic activity or environmental DNA·damaging agents (128). Spontaneous DNA modifications are mainly due to an intrinsic instability of the glycosyl bond between the base and the sugar moiety of a nucleotide or are induced by chemical cellular processes such as oxidation, hydrolytic deamination or alkylation of nucleotides. Furthermore, chemical as well as physical agents in the cellular environment threaten the integrity and stability of DNA. A variety of chemical agents interact with or modify DNA, resulting in inter- and intra·strand crosslinks, single strand- and double strand breaks, oxidized nucleotides, alkylated bases and sugars, bulky adducts on nucleotides, protein-DNA crosslinks and products intercalated into the double-helix. The most prominent physical DNA-damaging agents are v-rays, X-rays and UV-light. DNA damage can disturb vital cellular processes, whichdirectly depend on the integrity of DNA, such as transcription and replication. Blockage of the transcription of important housekeeping genes causes malfunctioning of the cell, which may result in cell death.
|Keywords||DNA repair, deficiency, molecular genetics, transcription|
|Promotor||Bootsma, D. (Dirk) , Hoeijmakers, J.H.J. (Jan)|
|Sponsor||Koningin Wilhelmina Fonds (KWF), Paes Nederland|
|Publisher||Erasmus MC: University Medical Center Rotterdam|
Vermeulen, W.. (1995, December 20). DNA repair and transcription deficiency syndromes. Erasmus MC: University Medical Center Rotterdam. Retrieved from http://hdl.handle.net/1765/22138