SLX4


Description

The SLX4 (SLX4 structure-specific endonuclease subunit) is a protein-coding gene located on chromosome 16.

SLX4 (also known as BTBD12 and FANCP) is a protein involved in DNA repair, where it has important roles in the final steps of homologous recombination. Mutations in the gene are associated with the disease Fanconi anemia. The version of SLX4 present in humans and other mammals acts as a sort of scaffold upon which other proteins form several different multiprotein complexes. The SLX1-SLX4 complex acts as a Holliday junction resolvase. As such, the complex cleaves the links between two homologous chromosomes that form during homologous recombination. This allows the two linked chromosomes to resolve into two unconnected double-strand DNA molecules. The SLX4 interacting protein interacts with SLX4 in the DNA repair process, specifically in interstrand crosslink repair. SLX4 also associates with RAD1, RAD10 and SAW1 in the single-strand annealing pathway of homologous recombination. The DNA repair function of SLX4 is involved in sensitivity to proton beam radiation.

SLX4 is a regulatory subunit that interacts with and increases the activity of various structure-specific endonucleases. It plays several roles in maintaining genome stability by resolving harmful DNA structures arising from replication, recombination, and DNA damage. SLX4 is part of the SLX1-SLX4 complex, a structure-specific endonuclease that resolves DNA secondary structures formed during DNA repair and recombination. SLX4 exhibits endonuclease activity against branched DNA substrates, introducing single-strand cuts in duplex DNA near junctions with ss-DNA. It shows a preference for 5'-flap structures and facilitates symmetrical cleavage of both static and migrating Holliday junctions (HJs), resolving them into two sets of ligatable, nicked duplex products. SLX4 interacts with the ERCC4-ERCC1 endonuclease to promote the cleavage of bubble structures and with the MUS81-EME1 endonuclease to promote the cleavage of 3'-flap and replication fork-like structures. SLX4 is essential for recovery from alkylation-induced DNA damage and participates in the resolution of DNA double-strand breaks.

SLX4 is also known as BTBD12, FANCP, MUS312.

Associated Diseases


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