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.
Keyphrases
- bone marrow
- dna damage
- stem cells
- circulating tumor
- poor prognosis
- oxidative stress
- single molecule
- chronic kidney disease
- induced apoptosis
- mesenchymal stem cells
- cell therapy
- dna repair
- squamous cell carcinoma
- acute myeloid leukemia
- signaling pathway
- radiation therapy
- locally advanced
- young adults
- replacement therapy
- cell cycle arrest
- circulating tumor cells
- squamous cell
- endoplasmic reticulum stress