Nucleotide excision repair, DNA

Brooks, P.J. (2008) The 8,5 -cyclopurine-2 -deoxynucleosides candidate neurodegenerafive DNA lesions in xeroderma pigmentosum, and unique probes of tianscription and nucleotide excision repair. DNA Repair, 7, 1168-1179. 

Crosslinks result from the reaction of a bifunctional electrophilic species with DNA bases and imply a covalent link between two adjacent DNA strands which inhibits DNA replication. Primary targets within bases are N7 and 06 in guanine and N3 in cytosine. The initial lesions are removed by the suicide enzyme alkyltrans-ferase, whereas nucleotide excision repair is needed for frilly established crosslinks. 

Figure 36-24. Nucleotide excision-repair. This mechanism is employed to correct larger defects in DNA and generally involves more proteins than either mismatch or base excision-repair. After defect recognition (indicated by XXXX) and unwinding of the DNA encompassing the defect, an excision nuclease (exinucle-ase) cuts the DNA upstream and downstream of the defective region. This gap is then filled in by a polymerase (5/e in humans) and religated.

Kasparkova, J. Zehnulova, J. Farrell, N. Brabec, V. DNA interstrand crosslinks of novel antitumor trinuclear platinum complex BBR. Conformation, recognition by HMG-domain proteins and nucleotide excision repair. J Biol Chem 2002, 277, 48076-48086. 

DNA base damage is also frequent after radiation (Ward, 1986). As compared to ssb, this DNA lesion is regarded as a possible source of mutation and is repaired through specific DNA repair pathways, such as base excision repair and nucleotide excision repair. 

Ultraviolet light induces the formation of dimers between adjacent thymines in DNA (also occasionally between other adjacent pyrimidines). The formation of thymine dimers interferes with DNA rephcation and normal gene expression. Thymine dimers are eliminated from DNA by a nucleotide excision-repair mechanism (Figure 1-2-4). 

Fig. 1. Proteins in DNA repair pathways. DNA repair proteins are listed for each of the following pathways BER (Base Excision Repair), NER (Nucleotide Excision Repair), MMR (Mismatch Repair), HR (Homologous Recombination), and NHEJ (Nonhomologous End Joining). PARP1/2 and BRCA1/2 are relevant in BER and HR pathways, respectively.

DNA repair pathways can be divided into those that respond to SSB and those that respond to DSB. SSB repair pathways include base excision repair (BER), mismatch repair (MMR), and nucleotide excision repair (NER). DSB repair pathways include nonhomologous end joining (NHEJ) and homologous recombination (HR). The proteins involved in these DNA repair pathways are shown in Fig. 1. 

DNA adducts most likely reflects increased DNA repair such as nucleotide excision repair and postreplication repair including translesion synthesis, gap filling, and template switching during replication (27,28). 

Nucleotide excision repair involves the removal of the region surrounding a modified base or single-strand break by nuclease-mediated excision (cutting) of the DNA strand on either side of the lesion followed by filling of the resulting gap. 

The answer is C. Thymine dimers are repaired by the process of nucleotide excision repair, which involves many enzyme activities that recognize the mutated structure, cut the DNA strand on both sides of the mutation, remove (excise) the affected fragment, and then refill the gap. One of the major genes leading to xeroderma pigmentosoum encodes a specific excinuclease. 

Tobacco accounts for about 90% of lung cancers. Some tobacco carcinogens induce DNA adducts that are repaired by the nucleotide excision repair (NER) pathway (3). The lowest DNA repair capacity (DRC), measured in peripheral blood lymphocytes by the host cell reactivation assay (HCR), was observed in lung cancer patients who were less than 60 years old, female, or lighter smokers, and in those with a family history of cancer (4,5). 

Hartman AR, Ford JM. BRCAl induces DNA damage recognition factors and enhances nucleotide excision repair. Nat Genet 2002 32 180-184. 

Indeed, Ellis s group provided some very nice examples of the application of Zn NMR spectroscopy when applied to proteins, such as the Minimal DNA Binding Domain of Human Nucleotide Excision Repair Protein XPA and the Human Carbonic Anhydrase. ... 

Most microorganisms have redundant pathways for the repair of cyclobutane pyrimidine dimers— making use of DNA photolyase and sometimes base-excision repair as alternatives to nucleotide-excision repair—but humans and other placental mammals do not. This lack of a back-up to nucleotide-excision repair for the removal of pyrimidine dimers has led to speculation that early mammalian evolution involved small, furry, nocturnal animals with little need to repair UV damage. However, mammals do have a path-... 

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