AI Article Synopsis
- Schlafen 11 (SLFN11) helps make cancer cells more sensitive to certain medicines that damage DNA.
- SLFN11 can stick to single-stranded DNA and works better when a part of it is changed, which is known as dephosphorylation.
- The study found that changing specific parts of SLFN11 and another protein, SLFN13, affects their ability to help with drug sensitivity, revealing important details about how SLFN11 works.
Article Abstract
Schlafen (SLFN) 11 enhances cellular sensitivity to various DNA-damaging anticancer agents. Among the human SLFNs (SLFN5/11/12/13/14), SLFN11 is unique in its drug sensitivity and ability to block replication under DNA damage. In biochemical analysis, SLFN11 binds single-stranded DNA (ssDNA), and this binding is enhanced by the dephosphorylation of SLFN11. In this study, human cell-based assays demonstrated that a point mutation at the ssDNA-binding site of SLFN11 or a constitutive phosphorylation mutant abolished SLFN11-dependent drug sensitivity. Additionally, we discovered that nuclear SLFN13 with a point mutation mimicking the DNA-binding site of SLFN11 was recruited to chromatin, blocked replication, and enhanced drug sensitivity. Through generating multiple mutants and structure analyses of SLFN11 and SLFN13, we identified protein phosphatase 2A as a binding partner of SLFN11 and the putative binding motif in SLFN11. These findings provide crucial insights into the unique characteristics of SLFN11, contributing to a better understanding of its mechanisms.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10730379 | PMC |
| http://dx.doi.org/10.1016/j.isci.2023.108529 | DOI Listing |
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