Robust designation of meiotic crossover sites by CDK-2 through phosphorylation of the MutSγ complex

Haversat, Jocelyn; Woglar, Alexander; Klatt, K.; Akerib, Chantal C; Roberts, Veronica; Salazar, Catcher C.; Chen, Shin-Yu; Arur, Swathi; Villeneuve, Anne M.; Kim, Yumi

doi:10.1101/2021.08.31.458431

Cited by 3 publications

(3 citation statements)

References 81 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A similar model was proposed and further supporting experimental data were recently obtained in C. elegans 17,36 . Several additional pieces of evidence suggest that the joint control of COs by SC and HEI10 is conserved: In multiple species, HEI10 homologs also initially form multiple foci before eventually consolidating into a limited number of large foci that co-localize with COs [19][20][21][22]37 ; COs covary with SC length in many species 13 ; Variants that affect recombination rates in natural populations of diverse species involve genes that encode HEI10 homologs 38 .…”

Section: Articlesupporting

confidence: 86%

Joint control of meiotic crossover patterning by the synaptonemal complex and HEI10 dosage

et al. 2022

View full text Add to dashboard Cite

Meiotic crossovers are limited in number and are prevented from occurring close to each other by crossover interference. In many species, crossover number is subject to sexual dimorphism, and a lower crossover number is associated with shorter chromosome axes lengths. How this patterning is imposed remains poorly understood. Here, we show that overexpression of the Arabidopsis pro-crossover protein HEI10 increases crossovers but maintains some interference and sexual dimorphism. Disrupting the synaptonemal complex by mutating ZYP1 also leads to an increase in crossovers but, in contrast, abolishes interference and disrupts the link between chromosome axis length and crossovers. Crucially, combining HEI10 overexpression and zyp1 mutation leads to a massive and unprecedented increase in crossovers. These observations support and can be predicted by, a recently proposed model in which HEI10 diffusion along the synaptonemal complex drives a coarsening process leading to well-spaced crossover-promoting foci, providing a mechanism for crossover patterning.

show abstract

Section: Articlesupporting

confidence: 86%

Joint control of meiotic crossover patterning by the synaptonemal complex and HEI10 dosage

et al. 2022

View full text Add to dashboard Cite

show abstract

“…During meiosis, mechanical stress on chromosomes has been proposed to regulate the number and spatial patterning of recombination events (Kleckner et al, 2004; Zhang et al, 2014). More recently, diffusion-based coarsening models have been proposed to explain the patterning of meiotic crossovers (Zhang et al, 2018; Morgan et al, 2021; Haversat et al, 2022) and—via RM and Mer2 condensates—DSBs (Claeys Bouuaert et al, 2021a). We therefore propose that the RM-TDB domain, with its intrinsic force-generating and force-responsive properties, is a fundamental building block that organizes meiotic recombination and that may reconcile mechanical stress and coarsening models for meiotic chromosome behavior.…”

Section: Discussionmentioning

confidence: 99%

Structure and DNA bridging activity of the essential Rec114–Mei4 trimer interface

Liu

Eliezer

et al. 2023

Preprint

View full text Add to dashboard Cite

The DNA double-strand breaks (DSBs) that initiate meiotic recombination are formed by an evolutionarily conserved suite of factors that includes Rec114 and Mei4 (RM), which regulate DSB formation both spatially and temporally. In vivo, these proteins form large immunostaining foci that are integrated with higher order chromosome structures. In vitro, they form a 2:1 heterotrimeric complex that binds cooperatively to DNA to form large, dynamic condensates. However, understanding of the atomic structures and dynamic DNA binding properties of RM complexes is lacking. Here, we report a structural model of a heterotrimeric complex of the C-terminus of Rec114 with the N-terminus of Mei4, supported by nuclear magnetic resonance experiments. This minimal complex, which lacks the predicted intrinsically disordered region of Rec114, is sufficient to bind DNA and form condensates. Single-molecule experiments reveal that the minimal complex can bridge two or more DNA duplexes and can generate force to condense DNA through long-range interactions. AlphaFold2 predicts similar structural models for RM orthologs across diverse taxa despite their low degree of sequence similarity. These findings provide insight into the conserved networks of protein-protein and protein-DNA interactions that enable condensate formation and promote formation of meiotic DSBs.

show abstract

“…To deplete CDK-2, we employed the auxin-inducible degradation system [71] and the cdk-2 (kim31[cdk-2::aid::3xflag]) allele [89]. Worms were grown on standard MYOB plates until they reached the L3 stage, at which point they were transferred to MYOB plates supplemented with 1mM indole-3-acetic acid (Alfa Aesar, Haverhill, MA) and seeded with E. coli OP50.…”

Section: Auxin Treatmentmentioning

confidence: 99%

The chromatin remodeling protein CHD-1 and the EFL-1/DPL-1 transcription factor cooperatively down regulate CDK-2 to control SAS-6 levels and centriole number

et al. 2022

View full text Add to dashboard Cite

Centrioles are submicron-scale, barrel-shaped organelles typically found in pairs, and play important roles in ciliogenesis and bipolar spindle assembly. In general, successful execution of centriole-dependent processes is highly reliant on the ability of the cell to stringently control centriole number. This in turn is mainly achieved through the precise duplication of centrioles during each S phase. Aberrations in centriole duplication disrupt spindle assembly and cilia-based signaling and have been linked to cancer, primary microcephaly and a variety of growth disorders. Studies aimed at understanding how centriole duplication is controlled have mainly focused on the post-translational regulation of two key components of this pathway: the master regulatory kinase ZYG-1/Plk4 and the scaffold component SAS-6. In contrast, how transcriptional control mechanisms might contribute to this process have not been well explored. Here we show that the chromatin remodeling protein CHD-1 contributes to the regulation of centriole duplication in the C. elegans embryo. Specifically, we find that loss of CHD-1 or inactivation of its ATPase activity can restore embryonic viability and centriole duplication to a strain expressing insufficient ZYG-1 activity. Interestingly, loss of CHD-1 is associated with increases in the levels of two ZYG-1-binding partners: SPD-2, the centriole receptor for ZYG-1 and SAS-6. Finally, we explore transcriptional regulatory networks governing centriole duplication and find that CHD-1 and a second transcription factor, EFL-1/DPL-1 cooperate to down regulate expression of CDK-2, which in turn promotes SAS-6 protein levels. Disruption of this regulatory network results in the overexpression of SAS-6 and the production of extra centrioles.

show abstract

Robust designation of meiotic crossover sites by CDK-2 through phosphorylation of the MutSγ complex

Cited by 3 publications

References 81 publications

Joint control of meiotic crossover patterning by the synaptonemal complex and HEI10 dosage

Joint control of meiotic crossover patterning by the synaptonemal complex and HEI10 dosage

Structure and DNA bridging activity of the essential Rec114–Mei4 trimer interface

The chromatin remodeling protein CHD-1 and the EFL-1/DPL-1 transcription factor cooperatively down regulate CDK-2 to control SAS-6 levels and centriole number

Contact Info

Product

Resources

About