Distribution of ultraviolet-induced lesions in simian virus 40 DNA

Bourre, F.; Renault, Georges; Seawell, Patricia C.; Sarasin, Alain

doi:10.1016/s0300-9084(85)80071-7

Cited by 29 publications

(33 citation statements)

References 11 publications

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“…Histone-DNA crosslinks caused by UV irradiation occur at an extremely low yield compared to PD (34,35) and, therefore, are expected to have little influence on the distribution. The (6-4) photodimers are formed with an overall yield of -1/10th that of PD, although considerable variation has been observed in specific sequences (3,36,37). We have attempted to specifically map the location of(6-4) photodimers in our core DNA samples by using hot alkali treatment, which has been shown to cleave the DNA backbone at these sites (14,38).…”

Section: Discussionmentioning

confidence: 99%

UV-induced formation of pyrimidine dimers in nucleosome core DNA is strongly modulated with a period of 10.3 bases.

Gale

Nissen²,

Smerdon³

1987

Proc. Natl. Acad. Sci. U.S.A.

196

150

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a DNase I cut site was incorrectly given as a 3' phosphate. The liberation of fragments with 3' hydroxyls by this enzyme makes the charge of these fragments the same as that of those liberated by T4 polymerase-exonuclease. The latter fragments differ only by the presence of a PD (cyclobutane pyrimidine dimer) at the 3' end.Proc. Natl. Acad. Sci. USA Vol. 84, pp. 6644-6648, October 1987 Biochemistry UV-induced formation of pyrimidine dimers in nucleosome core DNA is strongly modulated with a period of 10.3 bases (UV photoproduct ABSTRACTWe have determined the distribution of the major UV-induced photoproducts in nucleosome core DNA using the 3'-*5' exonuclease activity of T4 DNA polymerase, which has been shown to stop digestion immediately 3' to UV-induced pyrimidine dimers. This assay is extremely sensitive since all DNA fragments without photoproducts (background) are reduced to small oligonucleotides, which can be separated from those fragments containing photoproducts. The results show that the distribution of UV-induced photoproducts (primarily cyclobutane dipyrimidines) is not uniform throughout core DNA but displays a striking 10.3 (± 0.1) base periodicity. Furthermore, this characteristic distribution of photoproducts was obtained regardless of whether nucleosome core DNA was isolated from UV-irradiated intact chromatin fibers, histone H1-depleted chromatin fibers, isolated mononucleosomes, or cells in culture. The yield of pyrimidine dimers along the DNA seems to be modulated in a manner that reflects structural features of the nucleosome unit, possibly core histone-DNA interactions, since this pattern was not obtained for UV-irradiated core DNA either free in solution or bound tightly to calcium phosphate crystals. Based on their location relative to DNase I cutting sites, the sites of maximum pyrimidine dimer formation in core DNA mapped to positions where the phosphate backbone is farthest from the core histone surface. These results indicate that within the core region of nucleosomes, histone-DNA interactions significantly alter the quantum yield of cyclobutane dipyrimidines, possibly by restraining conformational changes in the DNA helix required for formation of these photoproducts.Irradiation by UV light produces a variety of lesions in cellular DNA, which, if unrepaired, may have lethal, mutagenic, or carcinogenic effects (1). The major lesion produced is the cyclobutane pyrimidine dimer (PD) formed between adjacent pyrimidines (2, 3), and the photochemistry of the formation of this lesion has been studied in detail (3). Several other photoproducts are also formed to a lesser extent. Among these are the pyrimidine-pyrimidone(6-4) adducts, which may play an important biological role since they have been shown to correlate with some mutational "hot spots" in specific DNA sequences (4).Since the "target" for PD formation in intact cells is DNA folded into the compact structure of chromatin (for reviews on chromatin structure, see refs. 5 and 6), it is important to understand the influence of...

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Section: Discussionmentioning

confidence: 99%

UV-induced formation of pyrimidine dimers in nucleosome core DNA is strongly modulated with a period of 10.3 bases.

Gale

Nissen²,

Smerdon³

1987

Proc. Natl. Acad. Sci. U.S.A.

196

150

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“…6; see also ref. 20), and generates the observed G-C to A-T transitions at cytosine. Readthrough does not readily explain the site-specific frequency of G-C to A-T transitions, because at site 43 or 124 fortuitously correct insertion of guanine opposite damaged cytosine would be required for two sterically dissimilar photoproducts.…”

Section: Resultsmentioning

confidence: 94%

Photoproduct frequency is not the major determinant of UV base substitution hot spots or cold spots in human cells.

Brash¹,

Seetharam²,

Kraemer³

et al. 1987

Proc. Natl. Acad. Sci. U.S.A.

208

112

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The role of UV radiation-induced photoproducts in initiating base substitution mutations in human cells was examined by measuring photoproduct frequency distributions and mutations in a supF tRNA gene on a shuttle vector plasmid transfected into DNA repair-deficient cells (xeroderma pigmentosum, complementation group A) and into normal cells. Frequencies of cyclobutane dimers and pyrimidine-pyrimidone (6-4) photoproducts varied by as much as 80-fold at different dipyrimidine sites within the gene. AU transition mutations occurred at dipyrimidine sites, predominantly at cytosine, with a 17-fold variation in mutation frequency between different sites. Removal of >99% of the cyclobutane dimers by in vitro photoreactivation before transfection reduced the mutation frequency while preserving the mutation distribution, indicating that (i) cytosine-containing cyclobutane dimers were the major mutagenic lesions at these sites and (ii) cytosinecontaining non-cyclobutane dimer photoproducts were also mutagenic lesions. However, at individual dipyrimidine sites neither the frequency of cyclobutane dimers nor the frequency of pyrimidine-pyrimidone (6-4) photoproducts correlated with the mutation frequency, even in the absence of excision repair. Mutation hot spots occurred at sites with low or high frequency of photoproduct formation and mutation cold spots occurred at sites with many photoproducts. These results suggest that although photoproducts are required for UV mutagenesis, the prominence of most mutation hot spots and cold spots is primarily determined by DNA structural features rather than by the frequency of DNA photoproducts.

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“…The good agreement between rates measured at different occurrences of each tetrad corroborates earlier reports that flanking bases strongly influence CPD yields under both low dose and high dose conditions. 10, 30, 40 …”

Section: Resultsmentioning

confidence: 99%

Sequence-dependent thymine dimer formation and photoreversal rates in double-stranded DNA

Law

Forties

Liu

et al. 2013

Photochem Photobiol Sci

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The kinetics of thymine-thymine cyclobutane pyrimidine dimer (TT-CPD) formation was studied at 23 thymine-thymine base steps in two 247-base pair DNA sequences irradiated at 254 nm. Damage was assayed site-specifically and simultaneously on both the forward and reverse strands by detecting emission from distinguishable fluorescent labels at the 5’-termini of fragments cleaved at CPD sites by T4 pyrimidine dimer glycosylase and separated by gel electrophoresis. The total DNA strand length of nearly 1000 bases made it possible to monitor damage at all 9 tetrads of the type XTTY, where X and Y are non-thymine bases. TT-CPD yields for different tetrads were found to vary by as much as an order of magnitude, but similar yields were observed at all instances of a given tetrad. Kinetic analysis of CPD formation at 23 distinct sites reveals that both the formation and reversal photoreactions depend sensitively on the identity of the nearest-neighbour bases on the 5’ and 3’ side of a photoreactive TT base step. The lowest formation and reversal rates occur when two purine bases flank a TT step, while the highest formation and reversal rates are observed for tetrads with at least one flanking C. Overall, the results show that the probabilities of CPD formation and photoreversal depend principally on interactions with nearest-neighbour bases.

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Distribution of ultraviolet-induced lesions in simian virus 40 DNA

Cited by 29 publications

References 11 publications

UV-induced formation of pyrimidine dimers in nucleosome core DNA is strongly modulated with a period of 10.3 bases.

UV-induced formation of pyrimidine dimers in nucleosome core DNA is strongly modulated with a period of 10.3 bases.

Photoproduct frequency is not the major determinant of UV base substitution hot spots or cold spots in human cells.

Sequence-dependent thymine dimer formation and photoreversal rates in double-stranded DNA

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