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Genetics and Genomics

Lymphoid-specific helicase in epigenetics, DNA repair and cancer

Subjects

Abstract

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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Fig. 1: LSH is a key regulator of chromatin structure and DNA-damage repair.
Fig. 2: The expression of LSH in various cancers.
Fig. 3: The roles of LSH in carcinogenesis.
Fig. 4: Domains of LSH homologs.

Data availability

Data analysed in Fig. 2 were extracted from the TCGA database (https://portal.gdc.cancer.gov/). The overall survival rate graph of NSCLC is from the study conducted by Mao et al., and the usage of the graph was approved (PMID: 30094095).

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Acknowledgements

We thank all the members of the laboratory for their resourceful comments on the manuscript.

Funding

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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YT, DX and GB contributed to the conception of the study; XC, Yamei Li and KR wrote the manuscript; BD, Yuyi Li and QT performed the data analyses; CM and SL helped with constructive discussions.

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Correspondence to Desheng Xiao or Guillermo Barreto or Yongguang Tao.

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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

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