Mutagenicity of a unique thymine-thymine dimer or thymine-thymine pyrimidine pyrimidone (6-4) photoproduct in mammalian cells

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The (6-4) photoproduct of thymine-thymine induces targeted substitution mutations in mammalian cells.

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. The DNAs replicated in the cells were recovered and were transfected again into Esche...

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The thymine-thymine pyrimidine-pyrimidone(6-4) ultraviolet light photoproduct is highly mutagenic and specifically induces 3' thymine-to-cytosine transitions in Escherichia coli.

We have constructed single-stranded, M13-based vectors that contain a specifically located thymine-thymine pyrimidine-pyrimidone(6-4) UV photoproduct and have used these to estimate the frequency and accuracy of DNA replication past this adduct in uvrA6 cells of Escherichia coli. Both the normal and the Dewar valence photoisomer of the (6-4) adduct were studied. In the absence of SOS induction,...

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UV-induced formation of the thymine-thymine pyrimidine (6-4) pyrimidone photoproduct--a DFT study of the oxetane intermediate ring opening.

The mechanism by which the hypothetical oxetane/azetidine intermediate formed during the photochemical process leading to pyrimidine (6-4) pyrimidone photoproducts when DNA is submitted to UV radiation opens is investigated computationally by DFT using a 5'-TT-3' dinucleoside monophosphate as a structural model. First, the feasibility of an intramolecular mechanism involving one proton transfer...

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Repair by human cell extracts of single (6-4) and cyclobutane thymine-thymine photoproducts in DNA.

One cis-syn cyclobutane thymine dimer or one (6-4) thymine-thymine photoproduct was built into an identical sequence of a closed-circular M13 duplex DNA, and nucleotide excision repair synthesis carried out by human cell extracts in the area containing each lesion was determined. Extracts from normal cells repaired the (6-4) photoproduct with a patch size of approximately 20-30 nucleotides, but...

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Mechanism of nucleotide incorporation opposite a thymine-thymine dimer by yeast DNA polymerase eta.

DNA polymerase eta (Poleta) has the unique ability to replicate through UV-light-induced cyclobutane pyrimidine dimers. Here we use pre-steady-state kinetic analyses to examine the mechanism of nucleotide incorporation opposite a cis-syn thymine-thymine (TT) dimer and an identical nondamaged sequence by yeast Poleta. Poleta displayed "burst" kinetics for nucleotide incorporation opposite both t...

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ژورنال

عنوان ژورنال: Nucleic Acids Research

سال: 1996

ISSN: 1362-4962

DOI: 10.1093/nar/24.10.1837