
@article {163313,
	title = {CTCF/cohesin-binding sites are susceptible to replication-associated DNA damage and genomic instability in cancer cells},
	journal = {iScience},
	volume = {29},
	year = {2026},
	month = {20 February 2026},
	pages = {114646},
	type = {Research Article},
	abstract = {<p><span style="color: rgb(31, 31, 31); font-family: ElsevierGulliver, Georgia, \&quot;Times New Roman\&quot;, Times, STIXGeneral, \&quot;Cambria Math\&quot;, \&quot;Lucida Sans Unicode\&quot;, \&quot;Microsoft Sans Serif\&quot;, \&quot;Segoe UI Symbol\&quot;, \&quot;Arial Unicode MS\&quot;, serif, sans-serif; font-size: 16px;">CTCF/cohesin-binding sites (CBSs) at the chromatin-loop anchors and topologically associating domains are frequently mutated in cancer; however, the underlying molecular mechanisms remain unclear. Here, we investigate whether CTCF and cohesin co-binding on DNA imposes constraints on DNA replication, leading to DNA damage and genomic instability. Our results reveal that CTCF and cohesin remain co-bound to DNA during replication in cancer cells (HeLa). Furthermore, analysis of DNA damage response/repair (DDR) proteins{\textemdash}including MRE11, STN1, γH2AX, and RAD51{\textemdash}showed a high enrichment of these proteins at CBSs, compared with immediate flanking regions. The loss of DDR genes in tumor genomes showed a significant enrichment of somatic mutations at CBSs compared with those tumors with intact DDR genes. Together, we propose that CTCF and cohesin co-binding can impede replication fork progression, leading to DNA damage and DDR activation. However, in cells with defective DDR, these lesions may promote genomic instability at CBSs.</span></p>
},
	keywords = {Bioinformatics, Cancer, Cell biology},
	doi = {https://doi.org/10.1016/j.isci.2026.114646},
	url = {https://www.sciencedirect.com/science/article/pii/S2589004226000210?via\%3Dihub},
	author = {Elangoli Ebrahimkutty Faseela and Dimple Notani and Radhakrishnan Sabarinathan}
}
