PARP4 deficiency enhances sensitivity to ATM inhibitor by impairing DNA damage repair in melanoma.

IF 6.1 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2025-01-30 DOI:10.1038/s41420-025-02296-0

Yuehua Li, Yu Liu, Jingjing Ma, Yuqi Yang, Qiao Yue, Guannan Zhu, Weinan Guo, Tianwen Gao, Qiong Shi, Chunying Li

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引用次数: 0

Abstract

Besides the important pathogenic mechanisms of melanoma, including BRAF-driven and immunosuppressive microenvironment, genomic instability and abnormal DNA double-strand breaks (DSB) repair are significant driving forces for its occurrence and development. This suggests investigating novel therapeutic strategies from the synthetic lethality perspective. Poly (ADP-ribose) polymerase 4 (PARP4) is known to be a member of the PARP protein family. The low expression of PARP4 is significantly associated with defective DSB repair markers and poor prognosis in melanoma. Further research revealed that PARP4 plays a role in DSB repair by regulating the non-homologous end joining (NHEJ) pathway through its involvement in Ku80 mono-ADP-ribosylation. Moreover, from a synthetic lethality perspective, PARP4 expression is associated with ATM inhibitor sensitivity. Overall, our study provides new and valuable insights into the function of PARP4 and melanoma pathogenesis and suggests that ATM inhibitor may be a promising therapeutic approach for treating melanoma with low PARP4 expression.

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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.