MutSβ regulates G4-associated telomeric R-loops to maintain telomere integrity in ALT cancer cells

Sakellariou, Despoina; Bak, Sara Thornby; Isik, Esin; Barroso, Sonia I; Porro, Antonio; Aguilera, Andrés; Bartek, Jiri; Janscak, Pavel; Peña-Diaz, Javier

doi:10.1016/j.celrep.2022.110602

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Sakellariou, D., Bak, S. T., Isik, E., Barroso, S. I., Porro, A., Aguilera, A., Bartek, J., Janscak, P., & Peña-Diaz, J. (2022). MutSβ regulates G4-associated telomeric R-loops to maintain telomere integrity in ALT cancer cells. Cell Reports, 39(1), 110602. https://doi.org/10.1016/j.celrep.2022.110602

Abstract

Up to 15% of human cancers maintain their telomeres through a telomerase-independent mechanism, termed "alternative lengthening of telomeres" (ALT) that relies on homologous recombination between telomeric sequences. Emerging evidence suggests that the recombinogenic nature of ALT telomeres results from the formation of RNA:DNA hybrids (R-loops) between telomeric DNA and the long-noncoding telomeric repeat-containing RNA (TERRA). Here, we show that the mismatch repair protein MutSβ, a heterodimer of MSH2 and MSH3 subunits, is enriched