SLX4 interacting protein is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

that in humans is encoded by the SLX4IP

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

Function

SLX4 interacting protein (SLX4IP) exists in a

monomer In chemistry, a monomer ( ; '' mono-'', "one" + ''-mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization. Classification ...

ic form, and interacts with the

SLX4 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 pres ...

- XPF-

ERCC1 DNA excision repair protein ERCC-1 is a protein that in humans is encoded by the ''ERCC1'' gene. Together with ERCC4, ERCC1 forms the ERCC1-XPF enzyme complex that participates in DNA repair and DNA recombination. Many aspects of these two gene ...

multiprotein complex, which is responsible for the assembly of a

Holliday junction resolvase Crossover junction endodeoxyribonuclease, also known as Holliday junction resolvase, Holliday junction endonuclease, Holliday junction-cleaving endonuclease, Holliday junction-resolving endoribonuclease, crossover junction endoribonuclease, and cru ...

in the role of DNA repair and maintenance. SLX4IP has been shown to directly interact with the N-terminal end of the

protein, which plays a role in the coordination of multiple different DNA structure-specific endonucleases. SLX4IP has also been shown to be involved in the control of alternative lengthening of

telomere A telomere (; ) is a region of repetitive nucleotide sequences associated with specialized proteins at the ends of linear chromosomes. Although there are different architectures, telomeres, in a broad sense, are a widespread genetic feature mos ...

s, through its accumulation and interactions with the

BLM BLM most commonly refers to: * Black Lives Matter, an international anti-racism movement and organization * Bureau of Land Management, a U.S. federal government agency BLM may also refer to: Organizations * BLM (law firm), United Kingdom and ...

and XPF proteins.

Location and expression

The SLX4IP gene is located on the short arm (p) of

chromosome 20 Chromosome 20 is one of the 23 pairs of chromosomes in humans. Chromosome 20 spans around 66 million base pairs (the building material of DNA) and represents between 2 and 2.5 percent of the total DNA in cells. Chromosome 20 was fully sequenced i ...

at position 12.2 (20p12.2). The human SLX4IP gene contains 14 exons, with the cDNA being 204,000 base pairs orientated on the plus strand. This codes for a protein of 408 amino acids with a molecular mass of 45,552 Daltons.

Homologs A couple of homologous chromosomes, or homologs, are a set of one maternal and one paternal chromosome that pair up with each other inside a cell during fertilization. Homologs have the same genes in the same loci where they provide points alon ...

of the SLX4IP gene have been found to be conserved in several non-human species including mice, rats, frogs, chickens, dogs, rhesus monkeys and chimpanzees.

Ortholog Sequence homology is the biological homology between DNA, RNA, or protein sequences, defined in terms of shared ancestry in the evolutionary history of life. Two segments of DNA can have shared ancestry because of three phenomena: either a s ...

s for the human SLX4IP gene have also been identified in 283 other organisms. The SLX4IP protein is expressed at its highest level in the skin and the testis, along with being expressed in 26 other tissues.

Clinical significance

Cancer

Acute lymphoblastic leukemia

Somatic and monoallelic deletions of the 5’ region of SLX4IP was shown to occur in 30% of patients with childhood acute lymphoblastic leukemia (ALL) and in cases of

ETV6 ETV6 (i.e. translocation-Ets-leukemia virus) protein is a transcription factor that in humans is encoded by the ''ETV6'' (previously known as ''TEL'') gene. The ETV6 protein regulates the development and growth of diverse cell types, particularly ...

RUNX1 Runt-related transcription factor 1 (RUNX1) also known as acute myeloid leukemia 1 protein (AML1) or core-binding factor subunit alpha-2 (CBFA2) is a protein that in humans is encoded by the ''RUNX1'' gene. RUNX1 is a transcription factor that re ...

-rearranged acute lymphoblastic leukemia, deletions were found in greater than 60% of cases. By analyzing the breakpoints of SLX4IP, characteristic illegitimate V(D)J mediated recombination was revealed. These deletions were found to be significantly biased towards the male gender.

Alternative lengthening of telomeres

In order for cancer cells to retain their ability to proliferate without limitations, they can regulate the

s of their chromosomes by recombination via a process known as alternative lengthening of telomeres (ALT). This recombination has been shown to require the accumulation of SLX4IP at ALT telomeres due to its antagonization of promiscuous

activity. BLM is responsible for the extension of telomeres as it is a

RecQ RecQ helicase is a family of helicase enzymes initially found in ''Escherichia coli'' that has been shown to be important in genome maintenance. They function through catalyzing the reaction ATP + H2O → ADP + P and thus driving the unwind ...

helicase vital to homologous recombination and DNA replication.

Interstrand crosslink repair

In DNA, Interstrand crosslinks (ICLs) are required to be repaired due to their high toxicity, often leading to diseases such as Fanconi anaemia. SLX4IP plays a role in the ICL repair functionality of the SLX4-XPF-ERCC1 complex, due to its simultaneous binding of both SLX4 and XPF-ERCC1, which maintains the stability of the complex and promotes interaction between the SLX4 and the XPF-ERCC1 regions. When SLX4IP was depleted from treated cells, they were found to accumulate in the G2/M phase of the cell cycle where the resolution of holiday junctions during ICL repair regularly occurs.

HIV-1

The

HIV-1 The subtypes of HIV include two major types, HIV type 1 (HIV-1) and HIV type 2 (HIV-2). HIV-1 is related to viruses found in chimpanzees and gorillas living in western Africa, while HIV-2 viruses are related to viruses found in the sooty mangabey ...

auxiliary protein

Vpr Vpr is a Human immunodeficiency virus gene and protein product. Vpr stands for "Viral Protein R". Vpr, a 96 amino acid 14-kDa protein, plays an important role in regulating nuclear import of the HIV-1 pre-integration complex, and is required for ...

potently stops the host cells progression through its natural cycle at the G2/M transition stage. This arrest was found to be caused from its premature activation of the SLX4 structure-specific endonuclease complex, which SLX4IP directly interacts with. Through this research the SLX4 complex was also discovered to be involved with the regulation of innate immunity, due to its negative regulation of type 1 interferon production, both when induced spontaneously and HIV-1-mediated.