6j0y

Structural highlights

Function

[RT107_YEAST] Required for resumption of chromosome replication after DNA damage, specifically in S phase. Is recruited to chromatin in the presence of RTT109 and RTT101 in response to stalled replication forks and acts as a scaffold during DNA repair.^{[1] [2]} [SLX4_YEAST] Regulatory subunit that interacts with and increases the activity of different structure-specific endonucleases. Has several distinct roles in protecting genome stability by resolving diverse forms of deleterious DNA structures. Component of the SLX1-SLX4 structure-specific endonuclease that resolves DNA secondary structures generated during DNA repair and recombination. Has endonuclease activity towards branched DNA substrates, introducing single-strand cuts in duplex DNA close to junctions with ss-DNA. Has a preference for simple Y, 5'-flap and replication fork-like structures. It cleaves the strand bearing the 5'-non-homologous arm at the branch site junction and generates ligatable, nicked products from the 5'-flap or replication fork substrates. Plays a critical role in maintaining the integrity of the ribosomal DNA (rDNA) loci, where it has a role in re-starting stalled replication forks. Has Holliday junction resolvase activity in vitro. Interacts with the structure-specific RAD1-RAD10 endonuclease and promotes RAD1-RAD10-dependent 3'-non-homologous tail removal (NHTR) during repair of double-strand breaks by single-strand annealing. SLX4 also promotes recovery from DNA-alkylation-induced replisome stalling during DNA replication by facilitating the error-free mode of lesion bypass. This does not require SLX1 or RAD1-RAD10, but probably RTT107.[HAMAP-Rule:MF_03110]^{[3] [4] [5] [6] [7] [8] [9] [10] [11]}

References

1. ↑ Rouse J. Esc4p, a new target of Mec1p (ATR), promotes resumption of DNA synthesis after DNA damage. EMBO J. 2004 Mar 10;23(5):1188-97. Epub 2004 Feb 26. PMID:14988729 doi:http://dx.doi.org/10.1038/sj.emboj.7600129
2. ↑ Roberts TM, Zaidi IW, Vaisica JA, Peter M, Brown GW. Regulation of rtt107 recruitment to stalled DNA replication forks by the cullin rtt101 and the rtt109 acetyltransferase. Mol Biol Cell. 2008 Jan;19(1):171-80. Epub 2007 Oct 31. PMID:17978089 doi:http://dx.doi.org/10.1091/mbc.E07-09-0961
3. ↑ Mullen JR, Kaliraman V, Ibrahim SS, Brill SJ. Requirement for three novel protein complexes in the absence of the Sgs1 DNA helicase in Saccharomyces cerevisiae. Genetics. 2001 Jan;157(1):103-18. PMID:11139495
4. ↑ Kaliraman V, Brill SJ. Role of SGS1 and SLX4 in maintaining rDNA structure in Saccharomyces cerevisiae. Curr Genet. 2002 Sep;41(6):389-400. Epub 2002 Aug 22. PMID:12228808 doi:http://dx.doi.org/10.1007/s00294-002-0319-6
5. ↑ Fricke WM, Brill SJ. Slx1-Slx4 is a second structure-specific endonuclease functionally redundant with Sgs1-Top3. Genes Dev. 2003 Jul 15;17(14):1768-78. Epub 2003 Jun 27. PMID:12832395 doi:http://dx.doi.org/10.1101/gad.1105203
6. ↑ Deng C, Brown JA, You D, Brown JM. Multiple endonucleases function to repair covalent topoisomerase I complexes in Saccharomyces cerevisiae. Genetics. 2005 Jun;170(2):591-600. doi: 10.1534/genetics.104.028795. Epub 2005, Apr 16. PMID:15834151 doi:http://dx.doi.org/10.1534/genetics.104.028795
7. ↑ Flott S, Rouse J. Slx4 becomes phosphorylated after DNA damage in a Mec1/Tel1-dependent manner and is required for repair of DNA alkylation damage. Biochem J. 2005 Oct 15;391(Pt 2):325-33. PMID:15975089 doi:http://dx.doi.org/BJ20050768
8. ↑ Roberts TM, Kobor MS, Bastin-Shanower SA, Ii M, Horte SA, Gin JW, Emili A, Rine J, Brill SJ, Brown GW. Slx4 regulates DNA damage checkpoint-dependent phosphorylation of the BRCT domain protein Rtt107/Esc4. Mol Biol Cell. 2006 Jan;17(1):539-48. doi: 10.1091/mbc.e05-08-0785. Epub 2005 Nov, 2. PMID:16267268 doi:http://dx.doi.org/10.1091/mbc.e05-08-0785
9. ↑ Flott S, Alabert C, Toh GW, Toth R, Sugawara N, Campbell DG, Haber JE, Pasero P, Rouse J. Phosphorylation of Slx4 by Mec1 and Tel1 regulates the single-strand annealing mode of DNA repair in budding yeast. Mol Cell Biol. 2007 Sep;27(18):6433-45. doi: 10.1128/MCB.00135-07. Epub 2007 Jul , 16. PMID:17636031 doi:http://dx.doi.org/10.1128/MCB.00135-07
10. ↑ Li F, Dong J, Pan X, Oum JH, Boeke JD, Lee SE. Microarray-based genetic screen defines SAW1, a gene required for Rad1/Rad10-dependent processing of recombination intermediates. Mol Cell. 2008 May 9;30(3):325-35. doi: 10.1016/j.molcel.2008.02.028. PMID:18471978 doi:http://dx.doi.org/10.1016/j.molcel.2008.02.028
11. ↑ Lyndaker AM, Goldfarb T, Alani E. Mutants defective in Rad1-Rad10-Slx4 exhibit a unique pattern of viability during mating-type switching in Saccharomyces cerevisiae. Genetics. 2008 Aug;179(4):1807-21. doi: 10.1534/genetics.108.090654. Epub 2008, Jun 24. PMID:18579504 doi:http://dx.doi.org/10.1534/genetics.108.090654