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Multiple functions of the ALT favorite helicase, BLM

Shun Chang, Tan Jiang, Ren Bao, Yanduo Zhang, Jinkai Tong, Tongxin Jia, Jing Liu, Juhua Dan, Shuting Jia

2025Cell & Bioscience8 citationsDOIOpen Access PDF

Abstract

Eukaryotic somatic cells undergo continuous telomere shortening because of end-replication problems. Approximately 10%~15% of human cancers rely on alternative lengthening of telomeres (ALT) to overcome telomere shortening. ALT cells are characterized by persistent telomere DNA replication stress and rely on recombination-based DNA repair pathways for telomere elongation. The Bloom syndrome (BLM) helicase is a member of the RecQ family, which has been implicated as a key regulator of the ALT mechanism as it is required for either telomere length maintenance or telomere clustering in ALT-associated promyelocytic leukemia bodies (APBs). Here, we summarize recent evidence detailing the role of BLM in the activation and maintenance of ALT. We propose that the role of BLM-dependent recombination and its interacting proteins remains a crucial question for future research in dissecting the molecular mechanisms of ALT.

Topics & Concepts

TelomereHelicaseHomologous recombinationBiologyRecQ helicaseDNA repairCell biologyGeneticsTelomere-binding proteinTelomeraseBloom syndromeGenome instabilityDNADNA damageDNA-binding proteinGeneRNATranscription factorTelomeres, Telomerase, and SenescenceDNA Repair MechanismsCRISPR and Genetic Engineering