SLX4 explained

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.^[1] Mutations in the gene are associated with the disease Fanconi anemia.^{[2] [3]}

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.^[4] The SLX4 interacting protein interacts with SLX4 in the DNA repair process, specifically in interstrand crosslink repair.^[5] SLX4 also associates with RAD1, RAD10 and SAW1 in the single-strand annealing pathway of homologous recombination.^[6] The DNA repair function of SLX4 is involved in sensitivity to proton beam radiation.^[7]

Notes and References

1. Klein HL, Symington LS . Breaking up just got easier to do . Cell . 138 . 1 . 20–22 . July 2009 . 19596231 . 10.1016/j.cell.2009.06.039 . 15429205 . free .
2. Kim Y, Lach FP, Desetty R, Hanenberg H, Auerbach AD, Smogorzewska A . Mutations of the SLX4 gene in Fanconi anemia . Nature Genetics . 43 . 2 . 142–146 . February 2011 . 21240275 . 3345287 . 10.1038/ng.750 .
3. van der Weyden L, White JK, Adams DJ, Logan DW . The mouse genetics toolkit: revealing function and mechanism . Genome Biology . 12 . 6 . 224 . June 2011 . 21722353 . 3218837 . 10.1186/gb-2011-12-6-224 . free .
4. Svendsen JM, Smogorzewska A, Sowa ME, O'Connell BC, Gygi SP, Elledge SJ, Harper JW . Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is required for DNA repair . Cell . 138 . 1 . 63–77 . July 2009 . 19596235 . 2720686 . 10.1016/j.cell.2009.06.030 .
5. Zhang H, Chen Z, Ye Y, Ye Z, Cao D, Xiong Y, Srivastava M, Feng X, Tang M, Wang C, Tainer JA, Chen J . 6 . SLX4IP acts with SLX4 and XPF-ERCC1 to promote interstrand crosslink repair . Nucleic Acids Research . 47 . 19 . 10181–10201 . November 2019 . 31495888 . 6821277 . 10.1093/nar/gkz769 .
6. Mimitou EP, Symington LS . DNA end resection: many nucleases make light work . DNA Repair . 8 . 9 . 983–995 . September 2009 . 19473888 . 2760233 . 10.1016/j.dnarep.2009.04.017 .
7. Liu Q, Underwood TS, Kung J, Wang M, Lu HM, Paganetti H, Held KD, Hong TS, Efstathiou JA, Willers H . 6 . Disruption of SLX4-MUS81 Function Increases the Relative Biological Effectiveness of Proton Radiation . International Journal of Radiation Oncology, Biology, Physics . 95 . 1 . 78–85 . May 2016 . 27084631 . 4889010 . 10.1016/j.ijrobp.2016.01.046 .