| 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). Upon DNA damage, inhibits translation of ATR or ATM based on distinct codon usage without disrupting early DNA damage response signaling (PubMed:30374083). Antiviral restriction factor with manganese-dependent type II tRNA endoribonuclease (PubMed:36115853). A single tRNA molecule is bound and cleaved by the SLFN11 dimer (PubMed:36115853). 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). Impairs the replication of human cytomegalovirus (HCMV) and some Flaviviruses (PubMed:35105802, PubMed:36115853). Exploits the unique viral codon bias towards A/T nucleotides (PubMed:23000900). Also acts as an interferon (IFN)-induced antiviral protein which acts as an inhibitor of retrovirus protein synthesis (PubMed:23000900).[1] [2] [3] [4] [5] [6] [7]
References
- ↑ 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:https://dx.doi.org/10.1073/pnas.1205943109
- ↑ 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:https://dx.doi.org/10.1038/nature11433
- ↑ 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:https://dx.doi.org/10.15252/embr.201540964
- ↑ 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:https://dx.doi.org/10.1016/j.molcel.2018.01.012
- ↑ Li M, Kao E, Malone D, Gao X, Wang JYJ, David M. DNA damage-induced cell death relies on SLFN11-dependent cleavage of distinct type II tRNAs. Nat Struct Mol Biol. 2018 Nov;25(11):1047-1058. PMID:30374083 doi:10.1038/s41594-018-0142-5
- ↑ Nightingale K, Potts M, Hunter LM, Fielding CA, Zerbe CM, Fletcher-Etherington A, Nobre L, Wang ECY, Strang BL, Houghton JW, Antrobus R, Suarez NM, Nichols J, Davison AJ, Stanton RJ, Weekes MP. Human cytomegalovirus protein RL1 degrades the antiviral factor SLFN11 via recruitment of the CRL4 E3 ubiquitin ligase complex. Proc Natl Acad Sci U S A. 2022 Feb 8;119(6):e2108173119. PMID:35105802 doi:10.1073/pnas.2108173119
- ↑ Metzner FJ, Wenzl SJ, Kugler M, Krebs S, Hopfner KP, Lammens K. Mechanistic understanding of human SLFN11. Nat Commun. 2022 Sep 17;13(1):5464. doi: 10.1038/s41467-022-33123-0. PMID:36115853 doi:https://dx.doi.org/10.1038/s41467-022-33123-0
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