Blood: SLFN11 promotes DNA replication fork degradation, which mediates the occurrence of van Nico anemia.

Van Coney anemia (FA) is a genetic disorder caused by a mutation in any of the 22 FA genes.
the disease is characterized by hypersensitivity to inter-chain crosslinking (ICL) inducers such as fissilemycin C (MMC).
in addition to promoting ICL repair, FA proteins such as RAD51, BRCA2, or FANCD2 protect stalled replication forks from nuclear dissolution degradation during replication stress, which can have a profound effect on THEA's pathophysiology.
recent studies have shown that the expression of potential DNA/RNA anticycline SLFN11 in tumor cells is associated with cell death after chemotherapy.
, however, the underlying mechanism of SLFN11-mediated DNA damage sensitivity remains unclear.
SLFN11 is highly expressed in hematopoietic stem cells, the researchers speculate that the absence of SLFN11 may improve the dedication of FA cells.
in this study, Okamoto, among others, reported that SLFN11, a PD20 cell line that knocks out FANCD2 defects from FA patient sources, improved cell survival under ITL inducing agent therapy.
FANCD2-/-SLFN11-/-HAP1 cells also showed edgetular rescue, including lower levels of MMC-induced chromosomal fracture compared to FANCD2-/-cells.
, the researchers found that SLFN11 promoted widespread degradation of replication forks in FANCD2-/-cells. the
degradation process is mediated by nuclease Mre11 or DNA2 and relies on the activity of the SLFN11 ATP enzyme, and is accompanied by increased binding of RAD51 on the stagnant replication fork, which is consistent with the subsequent degradation of the RAD51 antinuclease recruitment and replication fork.
inhibition of SLFN11 protects newly synthesized DNA beams, even in wild cells.
conclusion: SLFN11 destroys the stability of the stagnant replication fork, a function that may be related to ineffective hemagemia in FA patients.
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