Characterizing BORIS dynamics at telomeres in a colon cancer cell model

Telomeres serve as protective caps to the ends of linear eukaryotic chromosomes, ensuring chromosomal stability and integrity. They consist of tandem repeats of the sequence 5’-TTAGGG-3’ and are bound by several cellular proteins that regulate telomere sequence homeostasis.1 Telomeres act as a physical protective barrier to the loss of vital portions of protein-coding DNA during normal cellular division, as chromosomal DNA will shorten during normal replication pathways. Shortened telomeres are detected by the cell and can initiate cell cycle arrest pathways that suppress cell division, ultimately suppressing replication of the entire genome as a method of protection against oncogenesis in cells that have accumulated mutations.1 Telomere maintenance and stability can be controlled through regulatory proteins binding to the subtelomere, the transitional region between the telomeric DNA and protein coding genes on the chromosome. Telomere repeats are transcribed, creating telomeric repeat encoding RNA (TERRA), that has been previously shown to regulate telomere length homeostasis.2 CTCF is a regulatory protein which has been shown to bind to the subtelomere and promote the transcription of TERRA. This regulatory pathway has been implicated in decreased levels of telomeric stability, which allows for the natural cellular aging process to occur.2 Cancer cells must hijack these normal cellular processes to maintain telomeric length and continue to proliferate, which may be associated with the expression of BORIS, a CTCF paralog.4 Due to their similar structures, BORIS may have the ability to bind to some known subtelomeric CTCF-binding sites5, but unlike CTCF, it is not ubiquitously expressed in all cells. Some cancer cells can turn on the expression of BORIS, but the implications of doing so are not well understood.3,4,5 Due to the uncertainty surrounding BORIS’s function, this thesis aims to characterize a role for BORIS in telomere maintenance in the colon cancer cell line HCT116.