| 2008 |
SHOC1 (Arabidopsis ortholog) is required for class I meiotic crossover formation; shoc1 mutants show striking reduction in CO number with normal early recombination (DMC1 foci) and synapsis completion. Double-mutant analysis showed SHOC1 acts in the same pathway as AtMSH5 (a ZMM protein). SHOC1 shows sequence similarity to the XPF endonuclease protein family, suggesting direct involvement in maturation of DNA intermediates leading to COs. |
Genetic mutant analysis in Arabidopsis, cytological DMC1 foci quantification, double-mutant epistasis analysis, sequence similarity analysis |
Current biology : CB |
High |
18812090
|
| 2011 |
Arabidopsis SHOC1 interacts with PTD (an ERCC1-like protein) through its XPF-like nuclease-(HhH)2 domain to form an XPF-ERCC1-like heterodimer required for class I interfering crossovers. Both SHOC1 and PTD are required for class-I-interfering COs alongside MSH4, MSH5, MER3, and MLH3. The authors propose that the human ortholog C9orf84 (SHOC1) forms an analogous heterodimer with Zip2 in yeast. |
Yeast two-hybrid assay, genetic mutant analysis, double-mutant epistasis |
Journal of cell science |
High |
21771883
|
| 2018 |
Purified recombinant human SHOC1 (an XPF/MUS81 family member with conserved ERCC4-(HhH)2 core structure) preferentially binds branched DNA molecules in vitro but apparently lacks in vitro endonuclease activity despite conserved catalytic domain. In SHOC1 hypomorphic mice, MLH1 chromosomal localization is reduced, chiasma formation is reduced, and cells arrest at metaphase I with lagging chromosomes. SHOC1 localizes to a subset of recombination sites, axial element formation and homologous pairing are normal, but synapsis is altered. SHOC1 interacts with TEX11, connecting SHOC1 to chromosome axis and crossover structure. |
In vitro DNA binding assay with purified recombinant protein, in vitro endonuclease assay (negative result for nuclease), cytological analysis of SHOC1 hypomorphic mice, Co-immunoprecipitation/interaction assay with TEX11 |
PLoS genetics |
High |
29742103
|
| 2018 |
MZIP2 (SHOC1 mammalian ortholog) is the mammalian ortholog of yeast Zip2. Complete MZIP2 knockout in mice causes sterility in both males and females and defects in repairing meiotic DNA double-strand breaks. MZIP2 forms discrete foci on chromosome axes and is required for localization of TEX11 (mammalian Zip4 ortholog) and MSH4 to form crossover-prone recombination intermediates. In MZIP2-null meiocytes, crossover formation is abolished, synaptonemal complex formation is incomplete, and meiosis arrests at a zygotene-like stage. |
Mouse knockout, cytological analysis (foci localization, chromosome spreads), immunofluorescence |
Communications biology |
High |
30272023
|
| 2019 |
SPO16 (mammalian ortholog of yeast Spo16) physically interacts with SHOC1 (MZIP2/mammalian Zip2 ortholog) and forms a complex. SPO16 localizes to recombination nodules alongside SHOC1 and TEX11. SPO16 is required for stabilization of SHOC1 protein levels and proper localization of other ZMM proteins. In SPO16-deleted meiocytes, DSBs are repaired without CO formation though synapsis is less affected. The SPO16-SHOC1 complex-associated recombination intermediate is a key step facilitating meiotic recombination that produces COs. |
Co-immunoprecipitation, mouse KO, cytological localization studies, immunofluorescence |
Science advances |
High |
30746471
|
| 2022 |
Bi-allelic SHOC1 loss-of-function variants in NOA patients and Shoc1-knockout mice show meiotic defects including comprehensive defects in homologous pairing and synapsis, along with abnormal expression/localization of DMC1, RAD51, and RPA2 in spermatocyte spreads, suggesting SHOC1 has a presynaptic function during meiotic recombination in addition to its role in crossover formation. |
Whole-exome sequencing in patients, mouse KO (germ-cell-specific and general), meiotic chromosome spread analysis, immunofluorescence for DMC1/RAD51/RPA2 |
Molecular human reproduction |
Medium |
35485979
|
| 2022 |
M1AP interacts with the mammalian ZZS complex components SHOC1, TEX11, and SPO16. M1AP localizes to chromosomal axes in a SPO16-dependent manner. Ablation of M1AP does not alter SHOC1 localization but reduces the recruitment of TEX11 to recombination intermediates and decreases crossover formation in males. |
Co-immunoprecipitation, mouse KO, cytological immunofluorescence, chromosome spread analysis |
EMBO reports |
Medium |
36440627
|
| 2024 |
In RNF212B mutant mice, MZIP2 (SHOC1) localization to recombination intermediates is reduced, placing SHOC1 downstream of the RNF212B E3 ligase in the CO maturation pathway. |
Mouse KO of RNF212B, cytological immunofluorescence for MZIP2 foci |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
38865271
|
| 2023 |
FLIP-FIGNL1 complex promotes RAD51/DMC1 dissociation; FLIP-null meiocytes arrest at zygotene-like stage with massive RAD51 and DMC1 foci that frequently co-localize with SHOC1 and TEX11, indicating that SHOC1-positive recombination intermediates accumulate when RAD51/DMC1 are not properly dissociated. |
Mouse germline-specific KO, cytological co-localization immunofluorescence |
Nucleic acids research |
Low |
37439366
|
| 2025 |
In human SHOC1, the XPF-like domain is required for binding branched DNA structures and for CO formation. A missense variant (p.Q590R) within the XPF-like domain impairs DNA double-strand break repair by compromising branched DNA binding and recruitment of M1AP, REDIC1, and ZMM factors to recombination intermediates. The XPF-like domain also prevents autosome intrusion into the sex body, protecting autosomal loci from meiotic silencing of unsynapsed chromatin (MSUC). The variant disrupts 3D chromatin structure in pachytene spermatocytes and induces synapsis defects. |
Patient variant identification, in vitro DNA binding assay (branched DNA), cytological immunofluorescence, 3D chromatin analysis |
Nucleic acids research |
High |
42258546
|
| 2025 |
Men with ZZS (SHOC1/TEX11/SPO16) deficiency show early meiotic arrest with incorrect synapsis of homologous chromosomes, unrepaired DNA double-strand breaks, and incomplete recombination, phenotypically distinct from M1AP deficiency (which causes metaphase I arrest). This establishes SHOC1/ZZS function as essential for early meiotic recombination steps leading to synapsis in humans. |
In-depth testicular phenotyping of men with biallelic LoF variants, meiotic spread analysis, immunofluorescence |
EMBO molecular medicine |
Medium |
40374915
|
| 2023 |
During meiotic prophase I, SHOC1 binds to branched DNA and recruits SPO16 and other ZMM proteins to facilitate crossover formation (mechanistic model stated in context of SPO16 POI findings, consistent with prior experimental evidence from PMID:29742103 and PMID:30746471). |
Synthesis of experimental evidence cited in paper; SPO16 variant functional assay (minigene); prior biochemical data from referenced studies |
Clinical genetics |
Low |
37270785
|