RecQ Helicase Somatic Alterations in Cancer

Megha K Thakkar; Jamie Lee; Stefan Meyer; Vivian Y Chang

doi:10.3389/fmolb.2022.887758

RecQ Helicase Somatic Alterations in Cancer

Front Mol Biosci. 2022 Jun 15:9:887758. doi: 10.3389/fmolb.2022.887758. eCollection 2022.

Authors

Megha K Thakkar¹, Jamie Lee¹, Stefan Meyer^{2

3}, Vivian Y Chang^{1

4

5}

Affiliations

¹ Department of Pediatrics, Division of Pediatric Hematology-Oncology, University of California, Los Angeles, Los Angeles, CA, United States.
² Division of Cancer Studies, University of Manchester, Manchester, United Kingdom.
³ Department of Pediatric Hematology Oncology, Royal Manchester Children's Hospital and Christie NHS Foundation Trust, Manchester, United Kingdom.
⁴ Childrens Discovery and Innovation Institute, UCLA, Los Angeles, CA, United States.
⁵ Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, CA, United States.

Abstract

Named the "caretakers" of the genome, RecQ helicases function in several pathways to maintain genomic stability and repair DNA. This highly conserved family of enzymes consist of five different proteins in humans: RECQL1, BLM, WRN, RECQL4, and RECQL5. Biallelic germline mutations in BLM, WRN, and RECQL4 have been linked to rare cancer-predisposing syndromes. Emerging research has also implicated somatic alterations in RecQ helicases in a variety of cancers, including hematological malignancies, breast cancer, osteosarcoma, amongst others. These alterations in RecQ helicases, particularly overexpression, may lead to increased resistance of cancer cells to conventional chemotherapy. Downregulation of these proteins may allow for increased sensitivity to chemotherapy, and, therefore, may be important therapeutic targets. Here we provide a comprehensive review of our current understanding of the role of RecQ DNA helicases in cancer and discuss the potential therapeutic opportunities in targeting these helicases.

Keywords: BLM; RECQ1; RecQ helicases; Recql4; Recql5; WRN; cancer.

Publication types

Review