| 2006 |
Sws1 (ZSWIM7 ortholog) functions at an early pro-recombinogenic step of homologous recombination in fission yeast, forming a complex with Rlp1 and Rdl1 (RecA-like proteins most closely related to human XRCC2 and RAD51D). Inactivation of Sws1 suppresses the genotoxic sensitivity of srs2Δ and rqh1Δ mutants and rescues the inviability of srs2Δ rqh1Δ cells, placing Sws1 upstream of the antirecombinase activity of Srs2 and Rqh1. The human SWS1 homolog was shown to associate with RAD51D, and ablating SWS1 expression reduces the number of RAD51 foci. |
Genetic epistasis (suppressor analysis of srs2Δ rqh1Δ lethality), mass spectrometry-based interactome, co-immunoprecipitation (human SWS1–RAD51D), RAD51 focus formation assay |
The EMBO journal |
High |
16710300
|
| 2015 |
The SWIM domain of SWS1 (CXC…Xn…CXHXXA, extended to include an invariant alanine) is a zinc-binding motif essential for SWS1 function. In vivo disruption of invariant SWIM domain residues abolishes DNA damage tolerance in yeast and disrupts protein–protein interactions in both yeast and human cells. SWS1 is conserved from early-branching eukaryotes (Giardia) through C. elegans, Drosophila, and humans, and in humans it interacts with the RAD51 paralog SWSAP1. |
Site-directed mutagenesis of SWIM domain residues, DNA damage sensitivity assays (yeast), yeast two-hybrid and co-immunoprecipitation (human SWS1–SWSAP1), evolutionary/sequence analysis |
Genetics |
High |
25659377
|
| 2016 |
In C. elegans, SWS-1 promotes homologous recombination in both mitotic and meiotic nuclei. Direct interaction between SWS-1 and RIP-1 (RAD51 paralog) is mediated by the SWIM domain of SWS-1 and the Walker B motif of RIP-1. RIP-1 bridges an interaction between SWS-1 and RFS-1, forming a trimeric Shu complex. Loss of sws-1 causes sensitivity to DSB-inducing agents and failure to form mitotic RAD-51 foci after camptothecin treatment. |
CRISPR-induced nonsense allele (loss-of-function), yeast two-hybrid assay (SWS-1–RIP-1 interaction; SWIM domain and Walker B mutants), RAD-51 focus formation assay, genotoxin sensitivity assays |
Genetics |
High |
26936927
|
| 2018 |
The mouse Shu complex SWS1–SWSAP1 promotes assembly of RAD51 and DMC1 recombinases on early meiotic HR intermediates. Loss of Swsap1 (and by extension the SWS1 complex) causes meiotic arrest in both sexes, reduced crossover formation, and infertility. Concomitant loss of CHK2 rescues female fertility without rescuing crossover numbers (crossover homeostasis). Concomitant loss of the BRCA2 C terminus aggravates meiotic defects in Swsap1 mutant spermatocytes, indicating overlapping roles. |
Mouse knockout (Sws1 and Swsap1 null), immunostaining of RAD51/DMC1 foci on meiotic chromosome spreads, genetic epistasis (Swsap1 × Chk2 double knockout; Swsap1 × Brca2ΔCT double mutant) |
Nature communications |
High |
30305635
|
| 2021 |
The human SWS1–SWSAP1–SPIDR complex controls distinct types of homology-directed repair (HDR): it is required for stable RAD51 assembly at DNA damage sites but is dispensable for intra-chromosomal HDR. It is specifically critical for inter-homolog HDR (first mitotic factor identified for this function), drives high-level sister-chromatid exchange, promotes long-range loss of heterozygosity, and impels poor growth of BLM-deficient cells. SWSAP1 loss prolongs Blm-mutant embryo survival. |
Knockout cell lines and mice, HDR reporter assays (intra- vs inter-chromosomal), sister-chromatid exchange assays, RAD51 focus formation, genetic epistasis (Swsap1 × Blm double mutant) |
Nature communications |
High |
34253720
|
| 2021 |
A homozygous frameshift mutation (c.231_232del) in human ZSWIM7 causes decreased meiotic recombination, spermatocyte maturation arrest at a pachytene-like stage with incomplete synapsis, and azoospermia. A corresponding mouse model recapitulated these defects (reduced recombination, meiotic arrest, azoospermia), providing functional evidence that ZSWIM7 is required for meiotic recombination in human spermatogenesis. |
Whole-exome sequencing, spermatocyte chromosome spreads (immunostaining for meiotic markers), mouse knock-in model with equivalent mutation |
Human reproduction (Oxford, England) |
Medium |
33713115
|
| 2022 |
Loss-of-function variants in ZSWIM7 (homozygous nonsense p.Ser58*) are associated with primary ovarian insufficiency (POI) in humans. ZSWIM7 shows highest expression in the fetal ovary at 15/16 weeks post-conception, coinciding with peak meiosis, and its temporal expression profile parallels other homologous recombination genes in the developing ovary. |
Genome sequencing with autosomal recessive variant filtering, qRT-PCR of human fetal gonad, RNA sequencing of fetal gonad developmental time series |
The Journal of clinical endocrinology and metabolism |
Medium |
34402903
|
| 2022 |
Homozygous deleterious variants in ZSWIM7 alter its DNA-binding region (based on in silico structural modelling), and are associated with absent puberty and prepubertal ovaries/uterus in two unrelated patients, supporting a role for ZSWIM7 in DNA damage response during meiosis and ovarian development. |
Exome sequencing, protein conservation analysis, in silico structural modelling of variants |
The Journal of clinical endocrinology and metabolism |
Low |
35218660
|
| 2022 |
A missense variant in ZSWIM7 [c.176C>T, p.(Ser59Leu)] causes non-obstructive azoospermia in males and primary ovarian insufficiency in females within the same consanguineous family, demonstrating that ZSWIM7 loss-of-function affects meiotic recombination in both sexes. |
Whole exome sequencing, clinical phenotyping of affected males and females |
European journal of medical genetics |
Low |
36202298
|
| 2025 |
The C. elegans Shu complex (RFS1–RIP1–SWS1 heterotrimer) preferentially binds DNA with an exposed 5′ end, particularly favoring fork-shaped double-stranded DNA. The trimer binds ATP and exhibits DNA-dependent ATPase activity; catalytic residues in the RFS1 subunit were identified by site-specific mutagenesis and validated. The Shu trimer remodels RAD51 filaments in an ATP-hydrolysis-dependent manner and stabilizes filaments in an ATP-binding-dependent manner. |
In vitro biochemical reconstitution of trimeric complex, DNA-binding assays, ATPase assays with site-specific mutagenesis of catalytic residues, fluorescence-based RAD51 filament remodeling assays |
bioRxivpreprint |
High |
bio_10.1101_2025.11.17.685403
|
| 2025 |
Novel pathogenic variants in SWS1/ZSWIM7 (c.22del, c.151C>T in addition to previously described variants) and in its partner SWSAP1 (homozygous c.353del frameshift) cause isolated POI. Functional IH-HR assays in mouse embryonic stem cells showed partial decrease or absence of inter-homolog homologous recombination activity in Sws1−/− or Swsap1−/− cells; the SWSAP1 truncation mutant was destabilized. This confirms that all three SWS1-complex members (SWS1/ZSWIM7, SWSAP1, SPIDR) are required for meiotic IH-HR and female fertility. |
Exome/genome sequencing, IH-HR reporter assay in mouse embryonic stem cells (Sws1−/− and Swsap1−/−), western blot (protein stability), in silico structural modelling |
Human reproduction (Oxford, England) |
Medium |
40991243
|
| 2025 |
In allotetraploid crucian-carp hybrid males, ZSWIM7 protein is specifically localized to the nuclei of early meiotic primary spermatocytes, as shown by immunofluorescence, supporting a direct role for ZSWIM7 at the site of meiotic recombination. |
Immunofluorescence localization in testicular sections, quantitative PCR |
Animals |
Low |
41594540
|