Investigating the role of the calcium binding protein CAB39 in the repair of DNA double-strand breaks and the maintenance of genome stability 公开

Valavala, Navya (Spring 2025)

Permanent URL: https://etd.library.emory.edu/concern/etds/j67315191?locale=zh
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Abstract

Genome instability is a hallmark of cancer. As such, the mechanisms by which cells maintain their genomic integrity are critical to understanding cancer pathophysiology as well as other related genetic disorders. Among the most cytotoxic forms of DNA damage are DNA double strand breaks (DSBs), which are primarily repaired by non-homologous end joining (NHEJ) and homologous recombination (HR). In this study, we identified the calcium binding protein 39 (CAB39) as a putative NHEJ regulator using a CRISPR-based chemogenomic profiling. We performed functional validation using in vitro cell survival assays and revealed that CAB39 depletion selectively increases the sensitivity of cancer cells to a subset of NHEJ-associated genotoxic agents, notably etoposide and high dose of doxorubicin. To further characterize the role of CAB39 in DSB repair, we employed a GFP-based HR reporter assay and found that CAB39 depletion impairs HR efficiency, suggesting a regulatory role for CAB39 beyond the NHEJ pathway. Additionally, pan-cancer expression and survival analyses revealed that CAB39 is differentially expressed across tumor types, with high CAB39 transcript levels correlating with poor prognosis in specific cancers, including lung adenocarcinoma and lung squamous cell carcinoma. Together, our study suggests that CAB39 acts as a context-dependent modulator of the DNA damage response and a potential prognostic biomarker in cancer.

Table of Contents

Background

Results and Figures

Discussion

Materials and Methods

References

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