Continuous double-strand break induction and their differential processing sustain chiasma formation during Caenorhabditis elegans meiosis

Hicks, Tara; Trivedi, Shalini; Eppert, Mikayla; Bowman, Richard; Tian, Hui; Dafalla, Amna; Crahan, Caroline; Smolikove, Sarit; Silva, Nicola

doi:10.1016/j.celrep.2022.111403

Cited by 7 publications

(4 citation statements)

References 62 publications

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“…The signal of RTEL-1 reappeared in late pachytene where the CO or NCO outcomes are visibly manifested and persisted through diplotene and diakinesis, indicating a role of RTEL-1 at late stages of meiotic prophase I. A recent study showed that SPO-11-mediated DSBs continuously form until mid-late pachytene during meiotic progression in C. elegans ( 69 ). DSBs formed at late stages are essential for CO formation.…”

Section: Discussionmentioning

confidence: 99%

COSA-1 mediated pro-crossover complex formation promotes meiotic crossing over in C. elegans

Yang,

Wang,

Liu

et al. 2024

Nucleic Acids Research

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Accurate chromosome segregation during meiosis requires the establishment of at least one crossover (CO) between each pair of homologous chromosomes. CO formation depends on a group of conserved pro-CO proteins, which colocalize at CO-designated sites during late meiotic prophase I. However, it remains unclear whether these pro-CO proteins form a functional complex and how they promote meiotic CO formation in vivo. Here, we show that COSA-1, a key component required for CO formation, interacts with other pro-CO factors, MSH-5 and ZHP-3, via its N-terminal disordered region. Point mutations that impair these interactions do not affect CO designation, but they strongly hinder the accumulation of COSA-1 at CO-designated sites and result in defective CO formation. These defects can be partially bypassed by artificially tethering an interaction-compromised COSA-1 derivate to ZHP-3. Furthermore, we revealed that the accumulation of COSA-1 into distinct foci is required to assemble functional ‘recombination nodules’. These prevent early CO-designated recombination intermediates from being dismantled by the RTEL-1 helicase and protect late recombination intermediates, such as Holliday junctions, until they are resolved by CO-specific resolvases. Altogether, our findings provide insight into COSA-1 mediated pro-CO complex assembly and its contribution to CO formation.

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Section: Discussionmentioning

confidence: 99%

COSA-1 mediated pro-crossover complex formation promotes meiotic crossing over in C. elegans

Yang,

Wang,

Liu

et al. 2024

Nucleic Acids Research

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“…Lastly, a recent study has shown that DSBs formed in mid to late pachytene are preferentially resected by EXO-1 and DNA-2 in C . elegans [ 78 ], so it is possible that DSBs at the center of the chromosomes might be processed by the EXO-1-DNA-2 machinery that acts late in pachytene to form COs.…”

Section: Discussionmentioning

confidence: 99%

“…Another possibility is that the cKUs might regulate either the timing of DSB processing or the recruitment of other regulators, and in the absence of the cKUs, RAD-51 foci are preferentially on the center of the chromosomes because incorrect proteins are being recruited to places where normally HR is not used. Lastly, a recent study has shown that DSBs formed in mid to late pachytene are preferentially resected by EXO-1 and DNA-2 in C. elegans [78], so it is possible that DSBs at the center of the chromosomes might be processed by the EXO-1-DNA-2 machinery that acts late in pachytene to form Cos.…”

Section: Dsb Detection By Cku-70/80 But Not Nhej Influences Rad-51 Lo...mentioning

confidence: 99%

Chromatin landscape, DSB levels, and cKU-70/80 contribute to patterning of meiotic DSB processing along chromosomes in C. elegans

et al. 2023

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Programmed DNA double-strand break (DSB) formation is essential for achieving accurate chromosome segregation during meiosis. DSB repair timing and template choice are tightly regulated. However, little is known about how DSB distribution and the choice of repair pathway are regulated along the length of chromosomes, which has direct effects on the recombination landscape and chromosome remodeling at late prophase I. Here, we use the spatiotemporal resolution of meiosis in the Caenorhabditis elegans germline along with genetic approaches to study distribution of DSB processing and its regulation. High-resolution imaging of computationally straightened chromosomes immunostained for the RAD-51 recombinase marking DSB repair sites reveals that the pattern of RAD-51 foci throughout pachytene resembles crossover distribution in wild type. Specifically, RAD-51 foci occur primarily along the gene-poor distal thirds of the chromosomes in both early and late pachytene, and on both the X and the autosomes. However, this biased off-center distribution can be abrogated by the formation of excess DSBs. Reduced condensin function, but not an increase in total physical axial length, results in a homogeneous distribution of RAD-51 foci, whereas regulation of H3K9 methylation is required for the enrichment of RAD-51 at off-center positions. Finally, the DSB recognition heterodimer cKU-70/80, but not the non-homologous end-joining canonical ligase LIG-4, contributes to the enriched off-center distribution of RAD-51 foci. Taken together, our data supports a model by which regulation of the chromatin landscape, DSB levels, and DSB detection by cKU-70/80 collaborate to promote DSB processing by homologous recombination at off-center regions of the chromosomes in C. elegans.

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“…Given that it takes 12-14 hours for the nuclei to travel from the mitotic tip to TZ [53][54][55][56] , we let the depleted animals recover for slightly longer (16 hours) to ensure that cells had enough time to enter meiosis. As shown in Fig.…”

Section: Fig 3a)mentioning

confidence: 99%

Distinct intersecting pathways link homolog pairing to initiation of meiotic chromosome synapsis

Blazickova,

Trivedi,

Bowman

et al. 2024

Preprint

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Faithful meiotic segregation requires pairwise alignment of the homologous chromosomes and Synaptonemal Complex assembly (SC) at their interface. Here, we investigate on new factors that promote and coordinate these events during C. elegans meiosis. We identify BRA-2 (BMP Receptor Associated family member 2) as an interactor of HIM-17, previously shown to promote double-strand break formation. We found that loss of bra-2 specifically impairs synapsis licensing without affecting homologs recognition, SC maintenance or chromosome movement. Double mutant analysis revealed a previously unrecognized role for HIM-17 in promoting homolog pairing under dysfunctional SC assembly, without perturbing nuclear envelope recruitment of factors required for chromosome movement. We provide evidence that bra-2 and him-17 act in distinct pathways, exerting partially redundant functions in SC licensing, as well as separable roles in regulating homologs pairing. Altogether, our findings unveil novel mechanisms that ensure stabilization of homologous chromosome interaction via SC licensing upon homology assessment.

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Continuous double-strand break induction and their differential processing sustain chiasma formation during Caenorhabditis elegans meiosis

Cited by 7 publications

References 62 publications

COSA-1 mediated pro-crossover complex formation promotes meiotic crossing over in C. elegans

COSA-1 mediated pro-crossover complex formation promotes meiotic crossing over in C. elegans

Chromatin landscape, DSB levels, and cKU-70/80 contribute to patterning of meiotic DSB processing along chromosomes in C. elegans

Distinct intersecting pathways link homolog pairing to initiation of meiotic chromosome synapsis

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