The enigmatic oncogene and tumor suppressor‐like properties of RAD54B: Insights into genome instability and cancer

Abstract

One of the major challenges to the cell is to ensure genome stability, which can be compromised through endogenous errors or exogenous DNA damaging agents, such as ionizing radiation or common chemotherapeutic agents. To maintain genome stability the cell has a multifaceted line of defense, including cell cycle checkpoints and DNA damage repair pathways. RAD54B is involved in many of these pathways and thus exhibits a role in maintaining and repairing genome stability following DNA damage. RAD54B is involved in cell cycle regulation after DNA damage and participates in homologous recombinational repair, which ensures the precise repair of the most deleterious DNA lesions, double-stranded breaks. This review focuses on structural aspects of RAD54B, molecular functions associated with its cellular roles in preventing genome instability, and how aberrant function contributes to oncogenesis. By understanding how aberrant RAD54B expression and/or function can contribute to oncogenesis, novel therapeutic approaches that specifically exploit these aberrant genetics are now being explored for precision medicine targeting. RAD54B represents an ideal candidate for synthetic genetic therapeutic approaches (synthetic dosage lethality or synthetic lethality), which are designed to target the specific genetics associated with cancer formation. These therapeutic approaches represent a precision-based approach, which is ideal as we are now entering the era of precision medicine.

Aberrant SKP1 Expression: Diverse Mechanisms Impacting Genome and Chromosome Stability

“…A fundamental assumption of gene copy number alterations is that they induce corresponding changes in gene expression and that SKP1 copy number gains and losses are expected to underlie aberrant SCF complex activity leading to cellular dysfunction, genome instability and potentially tumorigenesis. Indeed, strong positive correlations exist between copy number changes and mRNA expression for all 12 cancer types investigated ( Figure 3 ), and while the copy number alterations detailed above suggest SKP1 may encode both oncogene-like or tumor suppressor-like functions, these seemingly opposing activities are not specific to SKP1 and have been reported for other genes including TP53 ( Lane, 1984 ; Jenkins et al, 1985 ; Finlay et al, 1989 ), USP22 ( Jeusset and McManus, 2017 ), and RAD54B ( McAndrew and McManus, 2017 ).…”

Amplification of RAD54B promotes progression of hepatocellular carcinoma via activating the Wnt/β-catenin signaling

“…Further studies clarified that RAD54B belongs to SWI2/SNF2 helicase superfamily and is involves in modulating the DNA damage checkpoint response [10] and homologous recombination repair (HRR) pathway [11] . Accordingly, sequencing assay uncovered that multiple human cancers are implicated in alterations of RAD54B such as gene amplification, homozygous deletion and non-synonymous single nucleotide polymorphism [12] , [13] , [14] , [15] , [16] , [17] . Of note, wang et al.…”

Overexpression of the lncRNA AC012213.3 Promotes Proliferation, Migration and Invasion of Breast Cancer via RAD54B/PI3K/AKT Axis and is Associated with Worse Patient Prognosis

“…Since RAD54B ensures faithful and accurate repair of DNA damage, its overexpression and downregulation would perturb genomic instability which could confer oncogenic properties. 20 Previous data has shown that suppression of RAD54B could block proliferation and promote apoptosis of liver and lung cancer cells. 21 , 22 In addition, RAD54B could remarkably facilitate cancer progression in breast cancer.…”