Structural highlights
Function
SLX1_YEAST Catalytic subunit 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.[HAMAP-Rule:MF_03100][1] [2]
Publication Abstract from PubMed
The SLX1-SLX4 structure-specific endonuclease complex is involved in processing diverse DNA damage intermediates, including resolution of Holliday junctions, collapse of stalled replication forks and removal of DNA flaps. The nuclease subunit SLX1 is inactive on its own, but become activated upon binding to SLX4 via its conserved C-terminal domain (CCD). Yet, how the SLX1-SLX4 complex recognizes specific DNA structure and chooses cleavage sites remains unknown. Here we show, through a combination of structural, biochemical and computational analyses, that the SAP domain of SLX4 is critical for efficient and accurate processing of 5'-flap DNA. It binds the minor groove of DNA about one turn away from the flap junction, and the 5'-flap is implicated in binding the core domain of SLX1. This binding mode accounts for specific recognition of 5'-flap DNA and specification of cleavage site by the SLX1-SLX4 complex.
Structure specific DNA recognition by the SLX1-SLX4 endonuclease complex.,Xu X, Wang M, Sun J, Yu Z, Li G, Yang N, Xu RM Nucleic Acids Res. 2021 Jul 21;49(13):7740-7752. doi: 10.1093/nar/gkab542. PMID:34181713[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ 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
- ↑ 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
- ↑ Xu X, Wang M, Sun J, Yu Z, Li G, Yang N, Xu RM. Structure specific DNA recognition by the SLX1-SLX4 endonuclease complex. Nucleic Acids Res. 2021 Jul 21;49(13):7740-7752. PMID:34181713 doi:10.1093/nar/gkab542
