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Genetics and Genomics

Lymphoid-specific helicase in epigenetics, DNA repair and cancer

British Journal of Cancer volume 126, pages 165–173 (2022)Cite this article

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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.

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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.

Author information

Authors and Affiliations

  1. Department of Pathology, Xiangya Hospital, Central South University; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Hunan, China

    Xiangyu Chen, Yamei Li, Bi Deng, Yuyi Li, Qinwei Tang, Chao Mao, Desheng Xiao & Yongguang Tao

  2. NHC Key Laboratory of Carcinogenesis of Ministry of Health (Central South University); Cancer Research Institute, Central South University, Changsha, Hunan, China

    Xiangyu Chen, Yamei Li, Bi Deng, Yuyi Li, Qinwei Tang, Chao Mao, Desheng Xiao & Yongguang Tao

  3. Université de Lorraine, CNRS, Laboratoire IMoPA, UMR 7365, Nancy, France

    Karla Rubio & Guillermo Barreto

  4. Univ Paris Est Creteil, Gly-CRRET, Brain and Lung Epigenetics (BLUE), Creteil, France

    Karla Rubio & Guillermo Barreto

  5. Lung Cancer Epigenetic, Max-Planck-Institute for Heart and Lung Research, Bad Nauheim, Germany

    Karla Rubio & Guillermo Barreto

  6. International Laboratory EPIGEN, Universidad de la Salud del Estado de Puebla, Puebla, Mexico

    Karla Rubio & Guillermo Barreto

  7. Department of Oncology, Institute of Medical Sciences, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China

    Shuang Liu

  8. Department of Thoracic Surgery, Hunan Key Laboratory of Early Diagnosis and Precision Therapy in Lung Cancer and Second Xiangya Hospital, Central South University, Changsha, China

    Yongguang Tao

Authors
  1. Xiangyu Chen
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  2. Yamei Li
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  3. Karla Rubio
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  4. Bi Deng
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  5. Yuyi Li
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  6. Qinwei Tang
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  7. Chao Mao
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  8. Shuang Liu
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  9. Desheng Xiao
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  10. Guillermo Barreto
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  11. Yongguang Tao
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Contributions

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.

Corresponding authors

Correspondence to Desheng Xiao, 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 126, 165–173 (2022). https://doi.org/10.1038/s41416-021-01543-2

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  • DOI: https://doi.org/10.1038/s41416-021-01543-2

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