Dr. Beishline publishes article in Nature Communications

Dr. Kate Beishline
Dr. Kate Beishline, BAHS assistant professor, and her collaborators Olga Vladimirova, Stephen Tutton, Zhou Wang, Zhong Deng, and Paul M. Lieberman, have  published a paper entitled "CTCF Driven TERRA Transcription Facilitates Completion of Telomere DNA Replication" in Nature Communications.

Telomeres function as a protective nucleo-protein structure at the ends of linear chromosomes. They are composed of tandem TTAGGG nucleotide repeats bound by a series of specialized proteins meant to protect this repeat DNA and maintain its structural integrity. Transcription of telomere repeats can initiate at subtelomeric repeat elements generating a long non-coding RNA, telomere repeat encoding RNA (TERRA) who’s function is not fully understood. The essential genome regulator CCCTC-binding factor, CTCF, is a sequence specific DNA binding factor that has been implicated in maintaining telomere stability and regulating TERRA transcription through binding to consensus binding sites in the putative promotor of TERRA transcripts in subtelomeric sequences. Despite their role in protecting chromosomal material, the telomeres can obstruct the completion of chromosomal DNA replication, especially under conditions of replication stress. It is not fully understood how CTCF and its regulation of TERRA transcription may be contributing to telomere stability particularly during DNA replication when telomeres are prone to stress.
 
These studies utilized CRISPR/Cas9 gene editing to mutate CTCF binding sites at the putative start site of TERRA transcripts for a class of human subtelomeres in order to assess the functional importance of CTCF driven TERRA transcription. Telomeres lacking CTCF-driven TERRA exhibit loss of local telomere signals during replication and consequently exhibit defects during mitosis and increased genomic instability. Importantly, these phenotypes were rescued by turning on TERRA transcription in the absence of CTCF, suggesting CTCF’s primary function at the telomere is to promote transcription.
 
The findings of this paper demonstrate that CTCF-driven TERRA transcription acts in cis to facilitate telomere repeat replication and chromosome stability.  Not only do these studies create new associations between CTCF and telomere stability, but make interesting observations about the intersection of DNA replication and transcription in cell biology.

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