Repair synthesis of DNA

For normal cell growth and proliferation, the DNA must be protected from various types of damage. Such damage, induced, for example, by uv irradiation, can involve the chemical alteration of the DNA and, consequently, deleterious mutation. Cells are able to correct or repair such damage. One of the best-understood mechanisms of repair involves the synthesis of new DNA, which replaces the damaged portion. This is called repair synthesis of DNA. The extent of repair synthesis is very small in comparison with the DNA synthesis accompanying replication of the chromosomes. 

No. All DNA polymerases use the deoxynucleoside 5 -triphosphates to add new nucleotide units, one at a time, onto the 3 -hydroxyl terminus of the growing chain. The main differences between DNA polymerase I and III relates to the type and relative contribution each makes to replication and repair-synthesis of DNA. 

Replication refers to the reproduction, through the copying of template DNA strands, of complete chromosomes. In this case DNA synthesis is extensive. Repair synthesis of DNA is involved in correcting the damage (caused by physical or chemical treatments) within isolated portions of DNA. In this case, DNA synthesis is restricted to the immediate vicinity of the damage and is usually only minor in extent. 

J. Jose, Repair Synthesis of DNA in the Lens Epithelium Relevance for Cataractogenesis. Dissertation, University of Alabama, Birmingham, 1976. 

Synthesis of DNA lesions and DNA-lesion-containing oligonucleotides for DNA-repair studies 99S1085. 

The TS mediates the conversion of 2-deoxyuridine monophosphate (dUMP) into deoxythymidine monophosphate (dTMP). This enzymatic methylation reaction is a key step in the synthesis of DNA and involves a ternary complex between the substrate, the enzyme and the co-factor [methylene tetrahydrofolic acid (CH2FAH4)] (Fig. 24) [8,80,81], This transformation represents the sole de novo source of dTMP, a building block for DNA synthesis and repair [82]. 

Phenol was reported to induce DNA oxidative damage in human promyelocytic HL60 cells and to inhibit repair of radiation-induced chromosomal breaks in human leukocytes (Morimoto et al., 1976). However, it only slightly inhibited DNA repair synthesis and DNA replication synthesis in WI-38 human diploid fibroblasts (Poirier et al., 1975). 

While defects in protein XPD often cause typical XP symptoms, some defects in the same protein lead to trichothiodystrophy (TTD, brittle hair disease). The hair is sulfur deficient, and scaly skin (ichthyosis, Box 8-F), mental retardation, and other symptoms are observed.0 Like their yeast counterparts (proteins RAD3 and RAD25), XPB and XPD are both DNA helicases.0 They also constitute distinct subunits of the human transcription factor TFIIHP, which is discussed in Chapter 28. It seems likely that XPD is involved in transcription-coupled repair (TCR) of DNA.° °i-s This is a subpathway of the nucleotide excision repair (NER) pathway, which allows for rapid repair of the transcribed strand of DNA. This is important in tissues such as skin, where the global NER process may be too slow to keep up with the need for rapid protein synthesis. Transcription-coupled repair also appears to depend upon proteins CSA and CSB, defects which may result in the rare cockayne syndrome.13 0 4 11 Patients are not only photosensitive but have severe mental and physical retardation including skeletal defects and a wizened appearance. 

Additional nucleic acids as their triphosphates may add to the 3 end of the existing oligonucleotide. This entire process is catalyzed and controlled by DNA polymerases, a family of enzymes that can replicate and repair DNA. The synthesis of DNA is always performed in the 5 to 3 direction.2 Furthermore, oligonucleotide strands are written with the letters of the nucleic acid monomers, starting from the 5 end. Oligonucleotide abbreviations should be read with an open mind because the literature contains many slightly different notation styles. 

Studies (127) with normal human lymphocytes showed a close correlation between the repair mode of DNA synthesis and stimulation of poly(ADP-ribose) activity. Incubation of permeabilized normal human lymphocytes with DNA-damaging agents including bleomycin. 

The biochemical pathways involved in DNA repair and DNA synthesis overlap in several regards thus, drugs acting on the synthesis of DNA putatively also interfere with the repair of DNA damage after applica-... 

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