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.
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We thank all the members of the laboratory for their resourceful comments on the manuscript.
This work was supported by the National Natural Science Foundation of China [82072594, 81672787, YT; 82073097, 81874139, 81672991, S.Liu; 82002916, CM; 82073136, 81772927, DX], China Postdoctoral Science Foundation [2019 M652804, CM], Natural Science Foundation of Hunan Province [2020JJ5790, CM], Hunan Provincial Key Area R&D Programs [2019SK2253, YT], Postdoctoral Foundation of Central South University [220372, CM], Shenzhen Science and Technology Program [KQTD20170810160226082, YT], and Shenzhen Municipal Government of China [JCYJ20180507184647104, YT]. Guillermo Barreto was funded by the “Université Paris-Est Créteil” (UPEC, Créteil, France), the “Centre National de la Recherche Scientifique” (CNRS, France), “Délégation Centre-Est” (CNRS-DR6), the “Lorraine Université” (LU, France) through the initiative “Lorraine Université d’Excellence” (LUE) and the dispositive “Future Leader” and the “Deutsche Forschungsgemeinschaft” (DFG, Bonn, Germany) (BA 4036/4-1). Karla Rubio was funded by the “Consejo de Ciencia y Tecnología del Estado de Puebla” (CONCYTEP, Puebla, Mexico) through the initiative International Laboratory EPIGEN.
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Chen, X., Li, Y., Rubio, K. et al. Lymphoid-specific helicase in epigenetics, DNA repair and cancer. Br J Cancer (2021). https://doi.org/10.1038/s41416-021-01543-2