RecQ Helicase Somatic Alterations in Cancer

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.

BLM promotes malignancy in PCa by inducing KRAS expression and RhoA suppression via its interaction with HDGF and activation of MAPK/ERK pathway

“…BLM, an important member of the RecQ family of helicases, is associated with an increase in cancer predisposition (Thakkar et al 2022). It is known for its functions in DNA replication, repair and telomere maintenance (Rezazadeh 2013).…”

Case report: A novel mutation of RecQ-like helicase 5 in a Chinese family with early myocardial infarction, coronary artery disease, and stroke hemiplegia

“…The RecQ family of helicases represents one of the most highly conserved groups of 3′-5′ DNA helicases and is named after the prototype Escherichia coli RecQ, called RECQL1, BLM, WRN, RECQL4, and RECQL5. Biallelic mutations in these RecQ homologs, WRN, BLM, and RECQL4, have been previously reported to be associated with rare human genetic diseases characterized by chromosomal instability and cancer susceptibility ( Croteau et al, 2014 ; Thakkar et al, 2022 ). In 2022, Abu-Libdeh et al reported that RECQL1 mutations can induce impaired DNA damage repair ability and lead to RECON syndrome, a genome instability disorder ( Abu-Libdeh et al, 2022 ).…”

“…RECQL5 deficiency may disrupt RAD51 recombinase nucleoprotein filaments and lead to genome instability ( Hu et al, 2007 ; Andrs et al, 2020 ). Several studies have also indicated that RECQL5 was involved in multiple hereditary cancer susceptibility ( Tavera-Tapia et al, 2019 ; Xia et al, 2021 ; Thakkar et al, 2022 ).…”

The Expression Characteristics and Function of the RECQ Family in Pan-Cancer

“…Significant variations in mRNA and protein levels were observed among different types of cancer in RECQs. Earlier findings suggested that the RECQs expression showed notable differences between tumors and non-neoplastic conditions [ 38 ]. In tumors, somatic chromosomal deletions and replications are characterized by CNVs, indicating that it may serve as a fertile environment for acquired alterations in cancer cells [ 39 ].…”