REXO5 Promotes Genomic Integrity Through Regulating R-loop Using Its Exonuclease Activity

Overview

Journal Leukemia

Specialties Hematology
Oncology

Date 2024 Jul 30

PMID 39080354

Authors

Ye Jin Lee

Seo Yun Lee

Soomi Kim

Soo-Hyun Kim

Soo Hyeon Lee

Sungho Park

Jae Jin Kim

Dong-Wook Kim

Hongtae Kim

Affiliations

Soon will be listed here.

Abstract

Chronic myeloid leukemia (CML), caused by BCR::ABL1 fusion gene, is known to regulate disease progression by altering the expression of genes. However, the molecular mechanisms underlying these changes are largely unknown. In this study, we identified RNA Exonuclease 5 (REXO5/LOC81691) as a novel gene with elevated mRNA expression levels in chronic myeloid leukemia (CML) patients. Additionally, using the REXO5 knockout (KO) K562 cell lines, we revealed a novel role for REXO5 in the DNA damage response (DDR). Compared to wild-type (WT) cells, REXO5 KO cells showed an accumulation of R-loops and increased DNA damage. We demonstrated that REXO5 translocates to sites of DNA damage through its RNA recognition motif (RRM) and selectively binds to R loops. Interestingly, we identified that REXO5 regulates R-loop levels by degrading mRNA within R-loop using its exonuclease domain. REXO5 KO showed ATR-CHK1 activation. Collectively, we demonstrated that REXO5 plays a key role in the physiological control of R-loops using its exonuclease domain. These findings may provide novel insights into how REXO5 expression changes contribute to CML pathogenesis.

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