Sequence specificity of DNA cleavage by Bis(1,10-phenanthroline)copper(I): Effects of single base pair transitions on the cleavage of preferred pyrimidine-purine-pyrimidine triplets

Journal Article · Tue Apr 18 00:00:00 EDT 1989 · Biochemistry; (USA)

DOI:https://doi.org/10.1021/bi00434a019· OSTI ID:5607446

Veal, J M; Rill, R L ^[1]

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1. Florida State Univ., Tallahassee (USA)

The cleavage of DNA restriction fragments by bis(1,10-phenanthroline)copper(I) (((OP){sub 2}Cu{sup I}){sup +}) is sequence dependent: the trimer TAT is most strongly preferred, while the trimer TGT and tetramers TAAT, TAGT, and CAGT are strongly to moderately preferred. ((OP){sub 2}Cu{sup I}){sup +} cleavage of a series of oligonucleotide duplexes of the type 5'-CCCTPyPuPyCCCC-3'/3'-GGGAPuPyPuGGGG-5' (Py = pyrimidine; Pu = purine) was examined to determine the effects of purine substituents in the central triplet on specificity. The relative cleavage rates of different PyPuPy triplets in oligomers were similar to those observed for restriction fragments. The undecamer duplex containing the trimer TAT (TTATC) was most preferentially cleaved, predominantly at the central adenosine and the adjacent 3'-thymidine. Duplexes differing from TTATC by a single A{center dot}T {yields} G{center dot}C transition in the central triplet were cleaved at significantly reduced rates relative to TTATC, the order of preference being TAT > TGT > TAC > CAT. The guanine 2-amino group at positions 1 and 2, but not position 3, of a 5'-PyPuPy-3' trimer is implicated as a strong inhibitor of DNA binding by the copper-phenanthroline complex. The influence of the guanine 2-amino group and other features of the cleavage at PyPuPy triplets can be rationalized by a partial intercalation binding model in which one phenanthroline ring system intercalates into the DNA minor groove at the 5'-PyPu-3' step.

• OSTI ID: 5607446
• Journal Information: Biochemistry; (USA), Journal Name: Biochemistry; (USA) Vol. 28:8; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AROMATICS
ATP
AUTORADIOGRAPHY
AZAARENES
AZINES
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
CHEMICAL REACTIONS
COPPER COMPOUNDS
DAYS LIVING RADIOISOTOPES
DECOMPOSITION
DNA
DNA SEQUENCING
DNA-ASE
ENDONUCLEASES
ENZYMATIC HYDROLYSIS
ENZYMES
ESTERASES
EVEN-ODD NUCLEI
HETEROCYCLIC COMPOUNDS
HYDROLASES
HYDROLYSIS
ISOTOPES
LIGHT NUCLEI
LYSIS
NUCLEI
NUCLEIC ACIDS
NUCLEOTIDES
OLIGONUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHODIESTERASES
PURINES
PYRIMIDINES
RADIOISOTOPES
SOLVOLYSIS
STRUCTURAL CHEMICAL ANALYSIS
SULFUR 35
SULFUR ISOTOPES
TRANSITION ELEMENT COMPOUNDS