XPF activates break-induced telomere synthesis

• DOI: 10.1038/s41467-022-33428-0
• Publication Date: 2022-10-02T05:02:27Z
• Authors: Chia-Yu Guh; Hong-Jhih Shen; Liv WeiChien Chen; Pei-Chen Chiu; I-Hsin Liao; Chen-Chia Lo; Yunfei Chen; Yu-Hung Hsieh; Ting-Chia Chang; Chien-Ping Yen; Yi-Yun Chen; Tom Wei-Wu Chen; Liuh-Yow Chen; Ching-Shyi Wu; Jean-Marc Egly; Hsueh-Ping Cather...
• Keywords: 0301 basic medicine; 03 medical and health sciences; Science; Q; RNA; Telomere Homeostasis; DNA; Telomere; Endonucleases; Telomerase; Article

Abstract Alternative Lengthening of Telomeres (ALT) utilizes a recombination mechanism and break-induced DNA synthesis to maintain telomere length without telomerase, but it is unclear how cells initiate ALT. TERRA, telomeric repeat-containing RNA, forms RNA:DNA hybrids (R-loops) at ALT telomeres. We show that depleting TERRA using an RNA-targeting Cas9 system reduces ALT-associated PML bodies, clustering, lengthening. interactome reveals interacts with extensive subset repair proteins in cells. One interacting proteins, the endonuclease XPF, highly enriched telomeres recruited by R-loops induce damage response (DDR) independent CSB SLX4, thus triggers The attraction BRCA1 RAD51 requires XPF FANCM-deficient accumulate R-loops. Our results suggest activate DDR via promote homologous replication drive