Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.celrep.2021.109879

Repository Public URL： https://hdl.handle.net/2324/7173505

Publisher：DNA Repair  

Fanconi anemia (FA) is a hereditary disorder characterized by a deficiency in the repair of DNA interstrand crosslinks and the response to replication stress. Endogenous DNA damage, most likely caused by aldehydes, severely affects hematopoietic stem cells in FA, resulting in progressive bone marrow failure and the development of leukemia. Recent studies revealed that expression levels of SLFN11 affect the replication stress response and are a strong determinant in cell killing by DNA-damaging cancer chemotherapy. Because SLFN11 is highly expressed in the hematopoietic system, we speculated that SLFN11 may have a significant role in FA pathophysiology. Indeed, we found that DNA damage sensitivity in FA cells is significantly mitigated by the loss of SLFN11 expression. Mechanistically, we demonstrated that SLFN11 destabilizes the nascent DNA strands upon replication fork stalling. In this review, we summarize our work regarding an interplay between SLFN11 and the FA pathway, and the role of SLFN11 in the response to replication stress.

DOI： 10.1016/j.dnarep.2024.103733

Web of Science

Scopus

PubMed

Language：English   Publisher：Communications Biology  

The Schlafen (SLFN)11 gene has been implicated in various biological processes such as suppression of HIV replication, replication stress response, and sensitization of cancer cells to chemotherapy. Due to the rapid diversification of the SLFN family members, it remains uncertain whether a direct ortholog of human SLFN11 exists in mice. Here we show that mSLFN8/9 and hSLFN11 were rapidly recruited to microlaser-irradiated DNA damage tracks. Furthermore, Slfn8/9 expression could complement SLFN11 loss in human SLFN11 −/− cells, and as a result, reduced the growth rate to wild-type levels and partially restored sensitivity to DNA-damaging agents. In addition, both Slfn8/9 and SLFN11 expression accelerated stalled fork degradation and decreased RPA and RAD51 foci numbers after DNA damage. Based on these results, we propose that mouse Slfn8 and Slfn9 genes may share an orthologous function with human SLFN11. This notion may facilitate understanding of SLFN11’s biological role through in vivo studies via mouse modeling.

DOI： 10.1038/s42003-023-05406-9

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1038/s42003-023-05406-9.

Web of Science

Event date： 2023.12

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2023.11

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2023.6

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Event date： 2023.5

Language：Japanese  

Country：Japan  

Event date： 2023.5

Language：Japanese   Presentation type：Oral presentation (general)  

Country：Japan  

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

Language：English   Publishing type：Article, review, commentary, editorial, etc. (scientific journal)  

DOI： https://doi.org/10.1530/ERC-16-0221

Repository Public URL： https://hdl.handle.net/2324/7178540

Type：Competition, symposium, etc. 

Type：Competition, symposium, etc.