Target intelligence / Profile preview

DNA repair and recombination protein RAD54-like (RAD54L) (RAD54L)

Target
RAD54L
Molecular classification
DNA-dependent ATPase, SNF2 family helicase, Chromatin remodeling factor, DNA repair protein
01

Overview

DNA repair and recombination protein RAD54-like (RAD54L) is a critical enzyme in the homologous recombination (HR) pathway, essential for repairing DNA double-strand breaks (DSBs) (UniProt P54277; NCBI Gene 5891). It belongs to the SNF2 family of DNA-dependent ATPases and functions by facilitating DNA strand exchange through interactions with the RAD51 recombinase and remodeling chromatin to allow access to repair templates (Tan et al., 1999, PMID: 10562555; Mazin et al., 2010, PMID: 20457804). In the context of oncology, RAD54L mRNA and protein are frequently overexpressed in various tumors, such as breast and colorectal cancers, where they contribute to therapeutic resistance by enhancing the cell's ability to repair damage from radiation or chemotherapy (Rossi et al., 2002, PMID: 12114443). Consequently, targeting RAD54L mRNA through RNA interference (siRNA) or antisense oligonucleotides is being investigated as a method to sensitize tumor cells to treatment by impairing their DNA repair capacity (Smirnova et al., 2004, PMID: 15105412). While there are currently no FDA-approved drugs specifically targeting RAD54L, it remains a significant target of interest for developing sensitizing agents and exploring synthetic lethal interactions in HR-deficient backgrounds (NCBI Gene 5891).

Other names
RAD54hHR54HR54RAD54ADNA repair and recombination protein RAD54-like
02

Mechanism of action

Inhibition of homologous recombination repair through mRNA degradation or protein activity blockade, leading to increased DNA damage and cell death.

03

Biological functions

Homologous recombinationDNA double-strand break repairChromatin remodelingDNA strand exchangeGenome stability
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Disease associations

CancerBreast cancerColorectal cancerLymphomaFanconi anemia-like syndrome
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Safety considerations

Potential for systemic toxicity due to inhibition of normal DNA repairGenomic instability in non-cancerous cellsOff-target effects of RNA interference
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Interacting drugs

Experimental siRNA

1 more in the full profile.

07

Biomarkers

RAD54L mRNA expression levelsRAD54L protein levelsHomologous recombination deficiency (HRD) status

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