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PMID:21743440

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Citation

Herrán, Y, Gutiérrez-Caballero, C, Sánchez-Martín, M, Hernández, T, Viera, A, Barbero, JL, de Álava, E, de Rooij, DG, Suja, JÁ, Llano, E and Pendás, AM (2011) The cohesin subunit RAD21L functions in meiotic synapsis and exhibits sexual dimorphism in fertility. EMBO J. 30:3091-105

Abstract

The cohesin complex is a ring-shaped proteinaceous structure that entraps the two sister chromatids after replication until the onset of anaphase when the ring is opened by proteolytic cleavage of its α-kleisin subunit (RAD21 at mitosis and REC8 at meiosis) by separase. RAD21L is a recently identified α-kleisin that is present from fish to mammals and biochemically interacts with the cohesin subunits SMC1, SMC3 and STAG3. RAD21L localizes along the axial elements of the synaptonemal complex of mouse meiocytes. However, its existence as a bona fide cohesin and its functional role awaits in vivo validation. Here, we show that male mice lacking RAD21L are defective in full synapsis of homologous chromosomes at meiotic prophase I, which provokes an arrest at zygotene and leads to total azoospermia and consequently infertility. In contrast, RAD21L-deficient females are fertile but develop an age-dependent sterility. Thus, our results provide in vivo evidence that RAD21L is essential for male fertility and in females for the maintenance of fertility during natural aging.

Links

PubMed PMC3160193 Online version:10.1038/emboj.2011.222

Keywords

Age Factors; Animals; Cell Cycle Proteins/metabolism; Chromosomal Proteins, Non-Histone/deficiency; Chromosomal Proteins, Non-Histone/metabolism; Chromosomes/metabolism; Female; Histocytochemistry; Infertility; Male; Meiosis; Mice; Mice, Knockout; Ovary/pathology; Protein Subunits/metabolism; Sex Factors; Testis/pathology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:RD21L

located_in

GO:0000800: lateral element

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:RD21L

acts_upstream_of_or_within

GO:0007283: spermatogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5292341

P

Seeded From UniProt

complete

MOUSE:RD21L

acts_upstream_of_or_within

GO:0007129: homologous chromosome pairing at meiosis

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5292341

P

  • occurs_in:(CL:0000017)

Seeded From UniProt

complete

MOUSE:RD21L

acts_upstream_of_or_within

GO:0006302: double-strand break repair

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5292341

P

  • occurs_in:(CL:0000017)

Seeded From UniProt

complete

MOUSE:RD21L

acts_upstream_of_or_within

GO:0070197: meiotic attachment of telomere to nuclear envelope

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:5292341

P

  • occurs_in:(CL:0000017)

Seeded From UniProt

complete

MOUSE:SYCP3

located_in

GO:0000800: lateral element

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000017)

Seeded From UniProt

complete

MOUSE:RAD51

located_in

GO:0000800: lateral element

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000017)

Seeded From UniProt

complete

MOUSE:REC8

located_in

GO:0000779: condensed chromosome, centromeric region

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000017)

Seeded From UniProt

complete

MOUSE:REC8

part_of

GO:0034991: nuclear meiotic cohesin complex

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000017)

Seeded From UniProt

complete

MOUSE:RFA1

located_in

GO:0000800: lateral element

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000017)

Seeded From UniProt

complete

MOUSE:SMC1B

part_of

GO:0034991: nuclear meiotic cohesin complex

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000017)

Seeded From UniProt

complete

MOUSE:SMC3

part_of

GO:0034991: nuclear meiotic cohesin complex

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000017)

Seeded From UniProt

complete

MOUSE:MLH1

located_in

GO:0005712: chiasma

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000017)

Seeded From UniProt

complete

MOUSE:MLH1

part_of

GO:0005712: chiasma

ECO:0000314: direct assay evidence used in manual assertion

C

part_of:(CL:0000017)

Seeded From UniProt

complete


See also

References

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