7zep

Structural highlights

Function

[SLN11_HUMAN] Inhibitor of DNA replication that promotes cell death in response to DNA damage (PubMed:22927417, PubMed:26658330, PubMed:29395061). Acts as a guardian of the genome by killing cells with defective replication (PubMed:29395061). Persistently blocks stressed replication forks by opening chromatin across replication initiation sites at stressed replication forks, possibly leading to unwind DNA ahead of the MCM helicase and block fork progression, ultimately leading to cell death (PubMed:29395061). Acts independently of ATR (PubMed:29395061). Also acts as an interferon (IFN)-induced antiviral protein which acts as an inhibitor of retrovirus protein synthesis (PubMed:23000900). Specifically abrogates the production of retroviruses such as human immunodeficiency virus 1 (HIV-1) by acting as a specific inhibitor of the synthesis of retroviruses encoded proteins in a codon-usage-dependent manner (PubMed:23000900). Binds to tRNAs and exploits the unique viral codon bias towards A/T nucleotides (PubMed:23000900). The exact inhibition mechanism is unclear: may either sequester tRNAs, prevent their maturation via post-transcriptional processing or may accelerate their deacylation (PubMed:23000900). Does not inhibit reverse transcription, integration or production and nuclear export of viral RNA (PubMed:23000900).^{[1] [2] [3] [4]}

References

1. ↑ Zoppoli G, Regairaz M, Leo E, Reinhold WC, Varma S, Ballestrero A, Doroshow JH, Pommier Y. Putative DNA/RNA helicase Schlafen-11 (SLFN11) sensitizes cancer cells to DNA-damaging agents. Proc Natl Acad Sci U S A. 2012 Sep 11;109(37):15030-5. doi:, 10.1073/pnas.1205943109. Epub 2012 Aug 27. PMID:22927417 doi:http://dx.doi.org/10.1073/pnas.1205943109
2. ↑ Li M, Kao E, Gao X, Sandig H, Limmer K, Pavon-Eternod M, Jones TE, Landry S, Pan T, Weitzman MD, David M. Codon-usage-based inhibition of HIV protein synthesis by human schlafen 11. Nature. 2012 Nov 1;491(7422):125-8. doi: 10.1038/nature11433. Epub 2012 Sep 23. PMID:23000900 doi:http://dx.doi.org/10.1038/nature11433
3. ↑ Mu Y, Lou J, Srivastava M, Zhao B, Feng XH, Liu T, Chen J, Huang J. SLFN11 inhibits checkpoint maintenance and homologous recombination repair. EMBO Rep. 2016 Jan;17(1):94-109. doi: 10.15252/embr.201540964. Epub 2015 Dec 9. PMID:26658330 doi:http://dx.doi.org/10.15252/embr.201540964
4. ↑ Murai J, Tang SW, Leo E, Baechler SA, Redon CE, Zhang H, Al Abo M, Rajapakse VN, Nakamura E, Jenkins LMM, Aladjem MI, Pommier Y. SLFN11 Blocks Stressed Replication Forks Independently of ATR. Mol Cell. 2018 Feb 1;69(3):371-384.e6. doi: 10.1016/j.molcel.2018.01.012. PMID:29395061 doi:http://dx.doi.org/10.1016/j.molcel.2018.01.012