cis-syn Thymine Dimer (CPD) Modified DNA Oligonucleotides

cis-syn Thymine Dimer, also known as a cis-syn cyclobutane pyrimidine dimer (CPD), is one of the most common DNA lesions generated by ultraviolet (UV) radiation. This photoproduct forms when two adjacent thymine residues on the same DNA strand undergo a [2+2] photocycloaddition reaction, creating a cyclobutane ring that covalently links the two pyrimidine bases.

The resulting cis-syn T<>T lesion alters the local geometry and hydrogen-bonding properties of DNA, potentially interfering with DNA replication, transcription, and protein recognition. Unlike a conventional phosphodiester backbone modification, the thymine dimer directly affects two neighboring nucleobases while leaving the DNA backbone intact.

cis-syn Cyclobutane pyrimidine dimers are important substrates for studying nucleotide excision repair (NER), the principal pathway responsible for removing UV-induced bulky DNA photoproducts in human cells. They are also recognized by CPD photolyases in organisms that possess photoreactivation pathways. Site-specifically modified oligonucleotides allow researchers to investigate DNA lesion recognition, repair efficiency, excision mechanisms, and interactions between damaged DNA and repair proteins.

During DNA replication, unrepaired thymine dimers can obstruct replicative DNA polymerases and promote recruitment of specialized translesion synthesis polymerases. For example, DNA polymerase eta can bypass cis-syn thymine dimers relatively efficiently, helping limit mutagenesis associated with UV-induced DNA damage. These properties make defined CPD-containing oligonucleotides valuable tools for investigating polymerase fidelity, DNA damage tolerance, and mutational mechanisms.

Unlike randomly UV-irradiated DNA, which may contain mixtures of cyclobutane pyrimidine dimers, (6-4) photoproducts, and other lesions, site-specifically synthesized cis-syn thymine dimer oligonucleotides provide a controlled substrate with a defined lesion position and sequence context. This enables more reproducible comparisons of DNA repair activity, polymerase bypass, protein binding, and lesion-dependent structural changes.

Bio-Synthesis offers custom DNA oligonucleotide synthesis incorporating cis-syn thymine dimer lesions for DNA damage and repair research, subject to sequence design, modified building-block availability, and synthesis feasibility. Custom constructs may include single-stranded lesion-containing DNA, complementary duplex substrates, fluorescently labeled repair probes, and other specialized DNA architectures.

Typical Applications

Nucleotide excision repair (NER) research
UV-induced DNA damage and photoproduct studies
DNA damage recognition and repair protein binding
CPD photolyase and photoreactivation assays
Translesion DNA synthesis and polymerase bypass
DNA polymerase eta activity and fidelity studies
UV-induced mutagenesis research
DNA replication and transcription-blocking studies
Structural analysis of lesion-containing DNA
Site-specific DNA damage substrates and molecular probes

Specifications & Technical Notes

Property	Specification / Notes
Modification	cis-syn Thymine Dimer
Full Chemical Name	cis-syn Cyclobutane Thymine-Thymine Dimer
Alternative Names	cis-syn CPD, cis-syn T<>T, cyclobutane thymine dimer, UV-induced thymine photodimer
Modification Code	[cis-syn-TT] or [CPD-TT]
Modification Type	UV-induced DNA photoproduct; covalent nucleobase lesion
Chemical Structure	Cyclobutane ring formed between the C5-C6 double bonds of two adjacent thymine bases
Number of Bases Affected	Two adjacent thymidine residues on the same DNA strand
Stereochemistry	cis-syn cyclobutane configuration; distinct from trans-syn CPD
Backbone Structure	The normal phosphodiester linkage between adjacent thymidines is retained
Synthesis Chemistry	Site-specific incorporation using a protected cis-syn thymine dimer dinucleotide phosphoramidite; alternative photochemical preparation and purification may be evaluated
Recommended Starting Material	Protected cis-syn thymine dimer phosphoramidite or a DNA precursor containing an adjacent TT site
Typical Modification Position	Internal adjacent TT site; terminal placement requires individual feasibility evaluation
Sequence Representation	5′-ACG[cis-syn-TT]GCA-3′; the bracketed lesion represents two thymidine residues
Molecular Mass Consideration	Cyclobutane dimer formation is an intramolecular photochemical reaction and produces no net change in elemental composition relative to the corresponding unmodified TT-containing DNA
Effect on DNA Structure	Alters local base geometry and hydrogen bonding; overall duplex distortion depends on lesion stereochemistry and sequence context
Effect on DNA Replication	Can inhibit replicative DNA polymerases; specialized translesion polymerases may bypass the lesion
DNA Repair Pathways	Nucleotide excision repair in human cells; photolyase-mediated photoreactivation in organisms possessing CPD photolyase
Lesion Recognition	Recognized by selected DNA repair proteins, including CPD-specific repair enzymes and nucleotide excision repair factors
Photoreversibility	Can undergo photoreversal under appropriate irradiation conditions or enzyme-mediated photoreactivation
Compatible DNA Formats	Single-stranded DNA, duplex DNA repair substrates, lesion-containing templates, and selected labeled constructs
Typical Applications	Nucleotide excision repair, DNA photodamage, photolyase assays, translesion synthesis, UV mutagenesis, polymerase bypass, and structural DNA research
Purification	HPLC or another validated separation method selected to resolve lesion-containing material from synthesis impurities and possible photoproduct isomers
Analytical Characterization	Mass spectrometry and chromatographic purity assessment; lesion identity may require additional confirmation because the CPD and unmodified TT sequence have the same molecular mass
Key Advantages	Defined lesion position, controlled sequence context, reproducible DNA repair substrates, and compatibility with mechanistic studies of UV-induced DNA damage
Storage	Store lyophilized at −20°C, protected from unnecessary UV exposure. Avoid repeated freeze-thaw cycles after reconstitution
Research Use	For research use only (RUO)

Product Information

Product Name:

cis-syn Thymine Dimer (CPD) Modified DNA Oligonucleotides

Category:

DNA Damage & Lesion Modifications

Modification Code:

[cis-syn-TT

Purification:

HPLC

Delivery Format:

Lyophilized

Shipping Conditions:

Room Temperature

Storage Conditions:

-20°C To -70°C
Oligonucleotides are stable in solution at 4°C for up to 2 weeks. Properly reconstituted material stored at -20°C should be stable for at least 6 months. Dried DNA (when kept at 20°C) in a nuclease-free environment should be stable for years.

References/Citations:

Selected References

Taylor JS, Brockie IR, O'Day CL. A building block for the sequence-specific introduction of cis-syn thymine dimers into oligonucleotides. Solid-phase synthesis of TpT[c,s]pTpT. Journal of the American Chemical Society. 1987;109(22):6735-6742. https://doi.org/10.1021/ja00256a030
Bdour HM, Kao JLF, Taylor JS. Synthesis and characterization of a [3-15N]-labeled cis-syn thymine dimer-containing DNA duplex. Journal of Organic Chemistry. 2006;71(4):1640-1646. https://doi.org/10.1021/jo0524167
Solid phase-supported thymine dimers for the construction of dimer-containing DNA by combined chemical and enzymatic synthesis: a potentially general method for the efficient incorporation of modified nucleotides into DNA. Nucleic Acids Research. 1997;25(19):3783-3788. https://doi.org/10.1093/nar/25.19.3783
Facile synthesis of a cis-syn thymine dimer building block and its incorporation into oligodeoxynucleotides. Tetrahedron. 2003. View publication
Chemical synthesis and translesion replication of a cis-syn cyclobutane thymine-uracil dimer. 2004. PubMed: 15020710