Proteomics

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Seeding the meiotic DNA break machinery and initiating recombination on chromosome axes


ABSTRACT: Recombination-mediated linking of homologous chromosomes is a unique meiotic feature that enables the halving of chromosomal ploidy in sexual life cycles. Meiotic recombination is initiated by programmed DNA double-strand breaks (DSBs) that are generated by focal multi-protein clusters that condense onto chromosomal axes by poorly understood mechanisms. We discovered in mice that a DBF4-dependent kinase (DDK)–modulated interaction between IHO1 and the chromosomal axis component HORMAD1 effects the formation of axis-bound IHO1 platforms that enhance nucleation of cytologically distinguishable DSB-machinery clusters. This IHO1-HORMAD1-mediated seeding of the DSB-machinery ensures that sufficient DSBs form for efficient pairing of homologous chromosomes. In the absence of IHO1-HORMAD1 interaction, residual DSB activity depends on ANKRD31, which enhances both the seeding and the growth of DSB-machinery clusters. Thus, meiotic DSBs are ensured by complementing pathways that differentially effect seeding and growth of DSB-machinery clusters, and that synergistically enable assembly of the DSB machinery on chromosomal axes.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Testis

SUBMITTER: Marc Gentzel  

LAB HEAD: Prof. Attila Toth

PROVIDER: PXD042179 | Pride | 2024-02-23

REPOSITORIES: Pride

Dataset's files

Source:
Action DRS
20201213_IHO10ul_RTSTD_16fm__060min_01.raw Raw
IHO_Phos_Analysis_Final_RG_Toth.pdf Pdf
IHO_Phos_Site_ID_Targeted_HR_Analysis_Final_RG_Toth.pdf Pdf
checksum.txt Txt
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