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Replication

During the DNA replication phase, i-motif forming sequences form the ability to regulate DNA replication in vivo, by producing a high stalling effect on DNA polymerase which hinders the process of replication or repair. The higher stalling effect of i-motif sequences hinder this process more than similar thermodynamic DNA structures such as hairpin structures due to i-motif's intercalating topology. The abstract intercalating topology of i-motif creates difficulty for unwinding resulting in the hinderance of DNA polymerase in DNA replication. The topology of the C-rich i-motif base pairs form intercalated parallel duplexes which reject unzipping, stalling DNA replication. The loop structures that also form in i-motif sequences may cause steric hinderance, disallowing DNA polymerase binding.

Human Telomeric DNA

The i-motif selective ligand, Carboxyl-modified single-walled carbon nanotubes (CSWNT), commonly binds to i-motif forming sequences. When bound to i-motif forming sequences produced by the C-rich telomeric DNA, CSWNT's have the ability to increase the thermal stability of i-motif under acidic conditions. The formation of i-motif structure is also promoted at pH 8.0 as the CSWNT's impede the formation of duplexes between the Watson Crick G·C base pairing (10). Within the telomeric region of DNA, i-motif sequences have inhibited and interfered with telomeric functions when bound. With the contribution of CSWNT's, the process of senescence and apoptosis of cancer cells is attainable seen in vivo and in vitro. This is caused by the C-rich telomeric strand forming an i-motif structure and the complementary G-rich strand forming a compact G-quadruplex. These formations result in the uncapping of telomeres and the agitation of telomeric structure causing telomere dysfunction (14). Furthermore, the shortening of telomeres due to telomerase activity can be inhibited by the formation of i-motif at the end of telomeres (23). As CSWNT's stabilize human telomeric i-motif structures while accompanied by complementary G-quadruplex formation, the uncapping of telomeres and interference of telomere-binding proteins (TRF2, POT1 and PCBP1) are attainable. This results in the conclusion of tumor cell growth within cancer cells.

Promoter Region

I-motif forming sequences can regulate the expression of genes in areas where promoter regions exist; this is found in more than 40% of all human genes.(7) I-motifs are also common in the promoters of genes which are characterized by skeletal system development and DNA processes such as sequence specific DNA binding, DNA templated transcription and positive regulation from RNA polymerase II (2).