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PMID:21478856

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Citation

Daniel, K, Lange, J, Hached, K, Fu, J, Anastassiadis, K, Roig, I, Cooke, HJ, Stewart, AF, Wassmann, K, Jasin, M, Keeney, S and Tóth, A (2011) Meiotic homologue alignment and its quality surveillance are controlled by mouse HORMAD1. Nat. Cell Biol. 13:599-610

Abstract

Meiotic crossover formation between homologous chromosomes (homologues) entails DNA double-strand break (DSB) formation, homology search using DSB ends, and synaptonemal-complex formation coupled with DSB repair. Meiotic progression must be prevented until DSB repair and homologue alignment are completed, to avoid the formation of aneuploid gametes. Here we show that mouse HORMAD1 ensures that sufficient numbers of processed DSBs are available for successful homology search. HORMAD1 is needed for normal synaptonemal-complex formation and for the efficient recruitment of ATR checkpoint kinase activity to unsynapsed chromatin. The latter phenomenon was proposed to be important in meiotic prophase checkpoints in both sexes. Consistent with this hypothesis, HORMAD1 is essential for the elimination of synaptonemal-complex-defective oocytes. Synaptonemal-complex formation results in HORMAD1 depletion from chromosome axes. Thus, we propose that the synaptonemal complex and HORMAD1 are key components of a negative feedback loop that coordinates meiotic progression with homologue alignment: HORMAD1 promotes homologue alignment and synaptonemal-complex formation, and synaptonemal complexes downregulate HORMAD1 function, thereby permitting progression past meiotic prophase checkpoints.

Links

PubMed PMC3087846 Online version:10.1038/ncb2213

Keywords

Animals; Cell Cycle Proteins/physiology; DNA Damage; DNA Repair; Meiosis; Mice

Significance

Annotations

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

MOUSE:HORM1

involved_in

GO:0007283: spermatogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HORM1

involved_in

GO:0007130: synaptonemal complex assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HORM1

involved_in

GO:0051598: meiotic recombination checkpoint signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HORM1

involved_in

GO:0051177: meiotic sister chromatid cohesion

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HORM1

involved_in

GO:0048477: oogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HORM1

involved_in

GO:0060629: regulation of homologous chromosome segregation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:HORM1

involved_in

GO:0042138: meiotic DNA double-strand break formation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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