한빛사논문
- 조회108
Ye Jin Lee1,5, Seo Yun Lee2,5, Soomi Kim1,5, Soo-Hyun Kim3,4, Soo Hyeon Lee2, Sungho Park1, Jae Jin Kim2, Dong-Wook Kim3,4 and Hongtae Kim1
1Department of Biological Sciences, Ulsan National Institute of Science and Technology, Ulsan, Republic of Korea.
2Department of Life Science and Multidisciplinary Genome Institute, Hallym University, Chuncheon, Republic of Korea.
3Department of Hematology, Hematology Center, Uijeongbu Eulji Medical Center, Eulji University, Uijeongbu, South Korea.
4Leukemia Omics Research Institute, Eulji University Uijeongbu Campus, Uijeongbu, South Korea.
5These authors contributed equally: Ye Jin Lee, Seo Yun Lee, Soomi Kim.
Correspondence and requests for materials should be addressed to Jae Jin Kim, Dong-Wook Kim or Hongtae Kim.
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.
논문정보
- Research article
- 2024년 07월 (BRIC 등록일 2024-07-31)
- 국내 연구진
- 바이오·의료융합 > 다학제 융합/복합
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