RAD52 and SLX4 act nonepistatically to ensure telomere stability during alternative telomere lengthening.

ABSTRACT: Approximately 15% of cancers use homologous recombination for alternative lengthening of telomeres (ALT). How the initiating genomic lesions invoke homology-directed telomere synthesis remains enigmatic. Here, we show that distinct dependencies exist for telomere synthesis in response to replication stress or DNA double-strand breaks (DSBs). RAD52 deficiency reduced spontaneous telomeric DNA synthesis and replication stress-associated recombination in G2, concomitant with telomere shortening and damage. However, viability and proliferation remained unaffected, suggesting that alternative telomere recombination mechanisms compensate in the absence of RAD52. In agreement, RAD52 was dispensable for DSB-induced telomere synthesis. Moreover, a targeted CRISPR screen revealed that loss of the st

SUBMITTER: Verma P 

PROVIDER: S-EPMC6362809 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature