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SLX1 HOMOLOG B, STRUCTURE-SPECIFIC ENDONUCLEASE SUBUNIT; SLX1B

SLX1 HOMOLOG B, STRUCTURE-SPECIFIC ENDONUCLEASE SUBUNIT; SLX1B

Alternative titles; symbolsSLX1 STRUCTURE-SPECIFIC ENDONUCLEASE SUBUNIT, S. CEREVISIAE, HOMOLOG OF, BGIY-YIG DOMAIN CONTAINING PROTEIN 2; GIYD2HGNC Approved Gene...

Alternative titles; symbols

  • SLX1 STRUCTURE-SPECIFIC ENDONUCLEASE SUBUNIT, S. CEREVISIAE, HOMOLOG OF, B
  • GIY-YIG DOMAIN CONTAINING PROTEIN 2; GIYD2

HGNC Approved Gene Symbol: SLX1B

Cytogenetic location: 16p11.2 Genomic coordinates (GRCh38): 16:29,454,500-29,458,218 (from NCBI)

▼ Cloning and Expression
By sequencing genomic clones from a 146-kb duplicated region of chromosome 16p, Hildebrandt et al. (2004) identified 2 copies of the SLX1 gene, SLX1A (615822) and SLX1B, which they referred to as MGC5178 copies. SLX1A and SLX1B share exons with the duplicated SULT1A3 (600641) and SULT1A4 (615819) genes, respectively. The SLX1 genes are transcribed in the same orientation as the SULT1A genes.

▼ Gene Structure
Hildebrandt et al. (2004) determined that the SLX1B gene contains 6 exons and overlaps the SULT1A4 gene, which is transcribed in the same orientation. Exons 3, 4, and 5 of SLX1B are used as SULT1A4 alternative exons 1D, 1C, and 1B, respectively. SULT1A4 exon 1E lies between SLX1B exons 1 and 2, but it is not found in SLX1B transcripts. An identical overlap of exons is found in the more centromeric SLX1A and SULT1A3 genes.

▼ Mapping
By genomic sequence analysis, Hildebrandt et al. (2004) mapped the SLX1B gene to chromosome 16p12.1, where it lies telomeric to the SLX1A gene on chromosome 16p11.2.

Gross (2014) mapped the SLX1B gene to chromosome 16p11.2 based on an alignment of the SLX1B sequence (GenBank BC000754) with the genomic sequence (GRCh37). SLX1B is located approximately 736 kb telomeric to SLX1A, which is also on chromosome 16p11.2.

▼ Gene Function
By analyzing proteins that purified with epitope-tagged SLX4 (613278) from human embryonic kidney cells, Svendsen et al. (2009) showed that SLX4 associated with the heterodimeric DNA flap endonucleases ERCC4 (133520)-ERCC1 (126380) and MUS81 (606591)-EME1 (610885) and the human ortholog of the yeast Slx1 endonuclease. In humans, 2 genes encode identical SLX1 proteins. SLX4 also associated with the telomere-interacting protein TERF2 (602027) and its partner TERF2IP (605061), the protein kinase PLK1 (602098), the MSH2 (609309)-MSH3 (600887) mismatch repair complex, and C20ORF94 (SLX4IP; 615958). Similar complexes were detected in other human cell lines examined. SLX1 associated with the extreme C terminus of SLX4. The SLX4 complex was recruited to sites of DNA damage and repaired 3-prime flap, 5-prime flap, and replication fork structures, consistent with the activities of the SLX4-associated DNA repair factors. The SLX1-SLX4 module specifically promoted symmetrical cleavage of static and migrating Holliday junctions. PLK1 phosphorylated SLX4 in situ, suggesting that phosphorylation of SLX4 regulates DNA repair by the SLX4 complex. Svendsen et al. (2009) concluded that the SLX4 complex is required for repair of specific types of DNA lesions and is critical for cellular responses to replication fork failure.

Using yeast 2-hybrid assays, Fekairi et al. (2009) showed that human SLX4 interacted with SLX1. Mutation analysis showed that the C-terminal domain of SLX4 was required for the interaction. The SLX1-SLX4 duplex functioned as a 5-prime flap endonuclease against a DNA stem loop substrate, and it resolved Holliday junctions into linear duplex products in the presence of Mn(2+). SLX1-SLX4 duplex activity was dependent on SLX1. However, SLX4, but not SLX1, was required for interstrand crosslink repair, suggesting that SLX4 functions with other endonucleases to repair interstrand crosslinks.

Tags: 16p11.2