Disease relevance of cyclobutane

• Recognition and repair of the cyclobutane thymine dimer, a major cause of skin cancers, by the human excision nuclease [1].
• Transcription-coupled repair removes both cyclobutane pyrimidine dimers and 6-4 photoproducts with equal efficiency and in a sequential way from transcribed DNA in xeroderma pigmentosum group C fibroblasts [2].
• All of these properties are the same as those previously reported for the E. coli ribosome crosslink that occurs via cyclobutane dimer formation between the 5' anticodon base 5'-carboxymethoxyuridine-34 and cytidine-1400 of the 16S RNA [3].
• We measured the kinetics of growth and mutagenesis of UV-irradiated DNA of phages S13 and lambda that were undergoing SOS repair; the kinetics strongly suggest that most of SOS mutagenesis arises from the deamination of cytosine in cyclobutane pyrimidine dimers, producing C----T transitions [4].
• UV endonuclease of Micrococcus luteus, a cyclobutane pyrimidine dimer-DNA glycosylase/abasic lyase: cloning and characterization of the gene [5].

High impact information on cyclobutane

• In mutant Arabidopsis plants that are deficient in photoreactivating ultraviolet-induced cyclobutane pyrimidine dimers, recombination under elevated UV-B regimes greatly exceeds wild-type levels [6].
• Here, RAD30 is shown to encode a DNA polymerase that can replicate efficiently past a thymine-thymine cis-syn cyclobutane dimer, a lesion that normally blocks DNA polymerases [7].
• M13 ss DNA molecules containing cyclobutane pyrimidine dimers were maintained but not replicated in Xenopus oocytes yet were replicated in progesterone-matured oocytes [8].
• Ligation-mediated polymerase chain reaction was used to analyze at nucleotide resolution the repair of cyclobutane pyrimidine dimers along the p53 gene in ultraviolet-irradiated human fibroblasts [9].
• Because studies of others have shown that photoreactivation repair monomerizes the ultraviolet-induced cyclobutane dimers in DNA, but does not affect the other photoproducts, these results indicate that DNA damage can influence the duration of clonal life-span unless that damage is repaired [10].

Chemical compound and disease context of cyclobutane

• The cyclobutane dimer photoproducts of dTpdC and dCpdT have been produced by acetophenone photosensitization and separated by reverse-phase HPLC [11].
• Spore photoproduct (SP) lyase from Bacillus subtilis specifically binds to and cleaves SP (5-thyminyl-5,6-dihydrothymine) but not cyclobutane pyrimidine dimers in UV-irradiated DNA [12].
• Synthesis of trans-1,2-cyclohexyldinitrilo tetramethylene phosphonic acid and its radiolabelling with 99mTc for the detection of skeletal metastases [13].
• Measurement of cyclobutane thymidine dimers in melanocytic nevi and surrounding epidermis in human skin in situ [14].
• To assess the adaptation induced by solar simulated radiation, we measured the proliferative response and cytokine production of skin-draining lymph node cells after immunization to DPCP, the contact hypersensitivity (CHS) response to PCl, and thymine-thymine (T-T) cyclobutane dimers in the skin of mice [15].

Biological context of cyclobutane

• UV-induced photoproducts (cyclobutane pyrimidine dimers, CPDs) in DNA are removed by nucleotide excision repair (NER), and the presence of transcription factors on DNA can restrict the accessibility of NER enzymes [16].
• These data indicate that with both CS and XP cyclobutane dimers are major photoproducts generating reduced plasmid survival and increased mutation frequency [17].
• Cyclobutane dimers were selectively removed before transfection by photoreactivation (PR), leaving nondimer photoproducts intact [17].
• Methylation of the 3'-cytosine in the sequence 5' CCAGG 3' reduces the yield of (6-4) lesions, but not of cyclobutane dimers, at these sites [18].
• The results show that the distribution of UV light-induced cyclobutane dimers within a defined sequence is similar whether the DNA is exposed to UV light as part of the chromosome of intact cells or as naked DNA [19].

Anatomical context of cyclobutane

• To address this, we established mammalian cell lines expressing Neurospora crassa UV damage endonuclease (UVDE), which introduces a SSB with a 3'-OH immediately 5' to UV-induced cyclobutane pyrimidine dimers or 6-4 photoproducts and initiates an alternative excision repair process [20].
• Insulin-like growth factor-1-mediated AKT activation postpones the onset of ultraviolet B-induced apoptosis, providing more time for cyclobutane thymine dimer removal in primary human keratinocytes [21].
• Our results suggest that in CHO cells the repair pathway for aminofluorene DNA adducts is not the same as that for cyclobutane dipyrimidines [22].
• Calf thymus proliferating cell nuclear antigen (PCNA) promoted DNA synthesis past cis-syn and trans-syn-I cyclobutane thymine dimers by calf thymus DNA polymerase delta (Pol delta) in vitro [23].
• Two major ultraviolet-induced photolesions of TpT, a (6-4) photoproduct [T(6-4)T] and a cis-syn cyclobutane TT dimer (T=T), were incorporated into a predetermined site of one of the leading and lagging template strands of a double-stranded vector, and the modified DNAs were transfected into simian COS-7 cells [24].

Associations of cyclobutane with other chemical compounds

• This increase in cyclobutane thymine removal resulted in enhanced survival if the amount of DNA damage was not too high [21].
• The sorbitol produced is most likely a result of the activity of aldose reductase, since (1) a low glucose concentration in the medium elicits this response, and (2) this activity is completely blocked by tetramethylene glutaric acid, a specific inhibitor of aldose reductase [25].
• Similarities and differences between cyclobutane pyrimidine dimer photolyase and (6-4) photolyase as revealed by resonance Raman spectroscopy: Electron transfer from the FAD cofactor to ultraviolet-damaged DNA [26].
• Sodium borohydride was used to covalently trap endonuclease V to a 49-base pair oligodeoxynucleotide containing a site-specific cyclobutane thymine dimer [27].
• Structural chemistry of cyclic nucleotides. IV. Crystal and molecular structure of tetramethylene phosphoric acid [28].

Gene context of cyclobutane

• The DDB2 gene, which is mutated in xeroderma pigmentosum group E, enhances global genomic repair of cyclobutane pyrimidine dimers and suppresses UV-induced mutagenesis [29].
• The repair of UV-induced photoproducts (cyclobutane pyrimidine dimers) in a well-characterized minichromosome, genomic DNA, and a transcribed genomic gene (RPB2) of a rad23delta mutant of Saccharomyces care was examined [30].
• In vivo recruitment of XPC to UV-induced cyclobutane pyrimidine dimers by the DDB2 gene product [31].
• To discriminate between both possibilities, we analyzed repair of UV-induced cyclobutane pyrimidine dimers at single base resolution in yeast cells lacking RAD26, the homolog of the Cockayne syndrome B gene [32].
• Binding of the MIG1 repressor to the glucose-repressible GAL1 and GAL4 promoters was analyzed in vivo by cyclobutane dimer footprinting in two yeast strains that show different glucose repression responses [33].

Analytical, diagnostic and therapeutic context of cyclobutane

• This was confirmed by gel analysis, a T4 UV endonuclease nicking assay specific for cyclobutane-type dimers, and HPLC analysis of the photoproducts [34].
• Sequence analysis of > 200 mutant plasmids showed that with CS cells a major mutational hot spot was caused by unrepaired cyclobutane dimers [17].
• This protein was identified using electrophoretic mobility shift assays of immunopurified UV-irradiated oligonucleotide substrates containing a single, site-specific cyclobutane pyrimidine dimer or a pyrimidine (6-4) pyrimidinone photoproduct [35].
• We studied the repair of UV-induced cyclobutane pyrimidine dimers at nucleotide resolution by ligation-mediated PCR [36].
• Radioimmunoassays that detect pyrimidine-pyrimidone (6-4) photoproducts and cyclobutane dimers were used to determine the relative induction of these photoproducts in nucleosomal (core) and internucleosomal (linker) DNA in human cell chromatin irradiated with UV light [37].

References