Lymphoid-specific helicase (LSH) is a member of the SNF2 helicase family of chromatin-remodelling proteins. Dysfunctions or mutations in LSH causes an autosomal recessive disease known as immunodeficiency-centromeric instability-facial anomaly (ICF) syndrome. Interestingly, LSH participates in various aspects of epigenetic regulation, including nucleosome remodelling, DNA methylation, histone modifications and heterochromatin formation. Further, LSH plays a crucial role during DNA-damage repair, specifically during double-strand break (DSB) repair, since murine LSH was shown to be essential for non-homologous end joining (NHEJ) and homologous recombination (HR). Accordingly, overexpression of LSH drives tumorigenesis and malignancy. On the other hand, LSH homologs stabilise the genome. Thus, LSH might be implemented as a biomarker for various cancer types and potential target molecule to develop therapeutic strategies against them. In this review, we focus on the role of LSH in orchestrating chromatin rearrangements, such as DNA methylation and histone modifications, as well as in DNA-damage repair. Changes in chromatin structure may facilitate gene expression signatures that cause malignant transformation. We summarise recent findings of LSH in cancers and raise critical open questions for further studies.

淋巴特异性解旋酶 (LSH) 是染色质重塑蛋白 SNF2 解旋酶家族的成员。 LSH 的功能障碍或突变会导致一种常染色体隐性遗传疾病，称为免疫缺陷-着丝粒不稳定-面部异常 (ICF) 综合征。有趣的是，LSH 参与表观遗传调控的各个方面，包括核小体重塑、DNA 甲基化、组蛋白修饰和异染色质形成。此外，LSH 在 DNA 损伤修复过程中发挥着至关重要的作用，特别是在双链断裂 (DSB) 修复过程中，因为小鼠 LSH 被证明对于非同源末端连接 (NHEJ) 和同源重组 (HR) 至关重要。因此，LSH 的过度表达会促进肿瘤发生和恶性肿瘤。另一方面，LSH 同源物稳定了基因组。因此，LSH 可以作为各种癌症类型的生物标志物和潜在的靶分子来开发针对这些癌症的治疗策略。在这篇综述中，我们重点关注 LSH 在协调染色质重排（例如 DNA 甲基化和组蛋白修饰）以及 DNA 损伤修复中的作用。染色质结构的变化可能促进导致恶性转化的基因表达特征。我们总结了 LSH 在癌症中的最新发现，并提出了进一步研究的关键开放问题。