Photochemistry of DNA and Polynucleotides: Photoproducts

Patrick, M. H.; Rahn, Ronald O.

doi:10.1016/b978-0-12-734602-1.50008-3

Cited by 183 publications

(117 citation statements)

References 136 publications

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“…There appeared to be photoproducts formed at virtually every pyrimidinepyrimidine site; formation at TT sites appeared to be more frequent than at CT and TC, and formation at these sites was more frequent than at CC sites. These results are consistent with the known relative frequencies of formation of cyclobutane pyrimidine dimers and 6-4 photoproducts (4,18).…”

Section: Resultssupporting

confidence: 80%

Sequence specificity of point mutations induced during passage of a UV-irradiated shuttle vector plasmid in monkey cells.

Hauser¹,

Seidman²,

Sidur³

et al. 1986

Mol. Cell. Biol.

170

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A simian virus 40-based shuttle vector was used to characterize UV-induced mutations generated in mammalian cells. The small size and placement of the mutagenesis marker (the supF suppressor tRNA gene from Escherichia cohl) within the vector substantially reduced the frequency of spontaneous mutations normally observed after transfection of mammalian cells with plasmid DNA; hence, UV-induced mutations were easily identified above the spontaneous background. UV-induced mutations characterized by DNA sequencing were found primarily to be base substitutions; about 56% of these were single-base changes, and 17% were tandem double-base changes. About 24% of the UV-induced mutants carried multiple mutations clustered within the 160-base-pair region sequenced. The majority (61%) of base changes were the G C-A -T transitions; the other transition (A * T-G C) and all four transversions occurred at about equal frequencies. Hot spots for UV mutagenesis did not correspond to hot spots for UV-induced photoproduct formation (determined by a DNA synthesis arrest assay); in particular, sites of TT dimers were underrepresented among the UV-induced mutations. These observations suggest to us that the DNA polymerase(s) responsible for mutation induction exhibits a localized loss of fidelity in DNA synthesis oi UV-damaged templates such that it synthesizes past UV photoproducts, preferentially inserting adenine, and sometimes misincorporates bases at undamaged sites nearby.Recent studies on viral and cellular oncogenes have provided strong evidence that mutations can play a fundamental role in cellular transformation and carcinogenesis (3). In addition, many heritable diseases and developmental anomalies have a mutational origin. Although numerous mutagenic agents are known to interact with DNA, the molecular mechanisms by which these agents may cause mutations in mammalian cells are not well understood. To approach this problem, we have used a UV-irradiated simian virus 40 (SV40)-based shuttle vector to analyze the sequence specificities of point mutations induced in mammalian cells by DNA damage. We reasoned that a detailed knowledge of the characteristics and spectrum of the mutations formed would provide information about the molecular mechanisms of mutation induction.In our previous work on the replication of UV-damaged SV40 DNA in mammalian cells (1,32,34), we demonstrated that replication of damaged templates appears to occur by a dimer-bypass mechanism in which replication forks proceed beyond UV-induced lesions, leaving gaps (single-strand discontinuities of 50 to 150 bases) in the daughter strands. Replication is completed at the normal terminus, and relaxed circular gapped molecules are produced. These gapped molecules are then slowly converted to SV40 form I DNA. We proposed that these single-strand gaps would be filled by DNA synthesis which might include insertion of mismatched bases at the sites of UV-induced lesions in the template strands, leading to the induction of point mutations at the damage sites. An alternat...

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Section: Resultssupporting

confidence: 80%

Sequence specificity of point mutations induced during passage of a UV-irradiated shuttle vector plasmid in monkey cells.

Hauser¹,

Seidman²,

Sidur³

et al. 1986

Mol. Cell. Biol.

170

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“…Specifically, the generally more single-stranded nature of the discontinuously replicated template strand may alter the formation of DNA photoproducts. Patrick and Rahn [6] and Bose and Davies [17] noted differences in the yields of different photoproducts under native (dsDNA) or denatured (ssDNA) conditions. Alternatively, our results may reflect differential processing by the DNA replication machinery.…”

Section: Discussionmentioning

confidence: 99%

“…UV produces a number of DNA photoproducts [5,6]; the cyclobutane pyrimidine dimer (CPD) and the pyrimidine photoproduct are responsible for much of the mutagenesis. CPDs may occur at any di-pyrimidine sequence; about 50% of the CPDs formed by germicidal UV (254 nm wavelength) involve TT sequences, while 40% involve TC or CT sequences and 10% involve CC sequences [6]. The photoproduct, in contrast, only forms readily at TT and TC sequences, and, overall, represents about 10% of the total photoproducts formed, although there is considerable site to site variability [7].…”

Section: Introductionmentioning

confidence: 99%

DNA sequence context affects UV-induced mutagenesis in Escherichia coli

Mak

Fix

2008

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

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We investigated the effect of altering the DNA sequence surrounding a mutable target site on the production of ultraviolet light (UV) induced mutations. Site-directed base substitutions were incorporated on both sides of a TAA sequence encoding a UAA nonsense defect in the tyrA14 allele of Escherichia coli. This allele is readily revertable by UV and a total of eight different base substitution mutations can be recovered. Five different strains harboring DNA sequences allowing the formation of 5′-TT, 5′-CT and 5′-TA* photoproducts were constructed and exposed to UV. DNA sequence analysis was used to determine the spectrum of the revertants that were recovered. The results showed that changes at the 3′ base of a TT site were predominately T to C transitions and T to A transversions. However, unlike the TT site, a 5′-CT site produced a relatively high frequency of T to G transversions. In addition, T to A transversions that could not have been targeted by a cyclobutane-type or [6-4]-type pyrimidine dimer were produced; this result suggested that these mutations may be targeted by a TA* photoproduct. Also, a distinct strand bias was noted for two mechanistically identical base substitutions in a strain having a palindromic target sequence; this result may reflect an unequal damage distribution or processing of photoproducts as a consequence of asymmetric DNA replication. Finally, our results show that DNA sequences expected to allow the greatest density of UV-induced DNA damage produce the highest mutation frequencies. Overall, these findings provide new insights regarding the role of DNA photoproducts in UV mutagenesis.

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“…Therefore, the change in DNA u.v. photochemistry on a/p-type SASP binding may be due less to the adoption of an A-like conformation and niore to factors such as exclusion of crucial water molecules from the DNA and/or inclusion of adjacent pyrimidines in a rigid structure thatdoes not allow reactions between them (Nicholson etai., 1991;Patrick and Gray, 1976;Patrick and Rahn, 1976). However, it is clear that the effects on the u.v.…”

Section: Small Acid-soluble Proteins Involved In A-dna Formation In Bmentioning

confidence: 92%

“…irradiation of complexes of a/p-type SASP with [^H]-thymine labelled DNA gives no CT or TT, but rather a 5-thyminyl-5,6-dihydrothymine adduct originally called spore photoproduct (SP) (Nicholson etai., 1991). SP is normally formed at significant levels only in dehydrated or frozen DNA, and its formation is favoured under conditions that promote formation of A-like DNA in vitro (Patrick and Gray, 1976;Patrick and Rahn, 1976).…”

Section: Small Acid-soluble Proteins Involved In A-dna Formation In Bmentioning

confidence: 99%

DNA in dormant spores of Bacillus species is in an A‐like conformation

Setlow

1992

Molecular Microbiology

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SummaryThe DNA in dormant spores of Bacillus species is associated with a/|3-type smaii, acid-soiuble proteins (SASP), which are double-stranded DNA-binding proteins whose amino acid sequence has been highly conserved in evolution. In vitro these proteins bind most strongly to DNA which readily adopts an A-iike conformation, as binding of a/|3-type SASP causes DNA to assume an A-like conformation. As predicted by this conformational change in DNA, binding of a/ptype SASP to relaxed but covalently closed plasmid DNA results in the introduction of a iarge number of negative supercoils. Associated with the conformational change in DNA brought about by oc/^-type SASP binding is a change in its photochemistry such that ultraviolet irradiation does not generate pyrimidine dimers, but rather a thyminyl-thymine adduct termed spore photoproduct (SP). The latter two properties of DNA complexed with o(/|3-type SASP in vitro are similar to those of DNA in dormant spores of Baciiius species in which: (i) plasmid DNA has a much higher number of negative supercoils than plasmid in growing cells; and (ii) ultraviolet irradiation produces SP and no pyrimidine dimers, while only pyrimidine dimers are formed in growing cells. During sporulation these changes in the properties of spore DNA take place in parallel with synthesis of a/ptype SASP, and the magnitude of the changes is greatly reduced in mutants that make low amounts of these proteins. A straightforward interpretation of these data is that DNA in dormant spores of Bacillus species is in an A-like conformation. DNA in an A-like conformation is also present in growing cells with high a/|3-type SASP levels. However, the presence of this A-like DNA is detrimental to cell growth.

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Photochemistry of DNA and Polynucleotides: Photoproducts

Cited by 183 publications

References 136 publications

Sequence specificity of point mutations induced during passage of a UV-irradiated shuttle vector plasmid in monkey cells.

Sequence specificity of point mutations induced during passage of a UV-irradiated shuttle vector plasmid in monkey cells.

DNA sequence context affects UV-induced mutagenesis in Escherichia coli

DNA in dormant spores of Bacillus species is in an A‐like conformation

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