Genetic dissection of MutL complexes in Arabidopsis meiosis
Nadia Kbiri1, Nadia Fernández-Jiménez2, Wojciech Dziegielewski1
1Laboratory of Genome Biology, Institute of Molecular Biology and Biotechnology, Adam Mickiewicz University, 61-614 Poznan, Poland.
Abstract:
During meiosis, homologous chromosomes exchange genetic material through crossing over. The main crossover pathway relies on ZMM proteins, including ZIP4 and HEI10, and is typically resolved by the MLH1/MLH3 heterodimer, MutLγ. Our analysis shows that while MUS81 may partially compensate for MutLγ loss, its role remains uncertain. However, our multiple mutant analysis shows that MUS81 is unlikely to be the sole resolvase of ZMM-protected recombination intermediates when MutLγ is absent. Comparing genome-wide crossover maps of mlh1 mutants with ZMM-deficient mutants and lines with varying HEI10 levels reveals that crossover interference persists in mlh1 but is weakened. The significant crossover reduction in mlh1 also increases aneuploidy in offspring. The loss of MutLγ can be suppressed by eliminating the FANCM helicase. Combined with the lower-than-expected chiasma frequency, this suggests that in MutLγ absence, some ZMM-protected intermediates are ultimately resolved by DNA helicases and/or their complexes with Top3α. Elevated MLH1 or MLH3 expression moderately increases crossover frequency, while their misregulation drastically reduces crossover numbers and plant fertility, highlighting the importance for tight control of MLH1/MLH3 levels. By contrast, PMS1, a component of the MutLα endonuclease, appears uninvolved in crossing over. Together, these findings demonstrate the unique role of MutLγ in ZMM-dependent crossover regulation.
Insights
The MutLγ (MLH1/MLH3) complex is crucial for resolving meiotic crossovers. Its absence leads to reduced crossovers, increased aneuploidy, and altered interference, highlighting its unique role in ZMM-dependent regulation.
Area of Science:
- Genetics
- Molecular Biology
- Cell Biology
Background:
- Meiotic recombination involves homologous chromosome exchange via crossing over.
- The ZMM protein pathway, including ZIP4 and HEI10, mediates crossovers.
- MutLγ (MLH1/MLH3) is the primary resolvase for ZMM-protected recombination intermediates.
Purpose of the Study:
- To elucidate the role of MutLγ in meiotic crossover resolution.
- To investigate alternative crossover resolution pathways in the absence of MutLγ.
- To understand the regulation and impact of MutLγ levels on crossover interference and aneuploidy.
Main Methods:
- Analysis of multiple mutants in meiotic recombination pathways.
- Genome-wide crossover mapping in mlh1 mutants and ZMM-deficient lines.
- Comparison of crossover frequencies and interference patterns under varying HEI10 and MLH1/MLH3 expression levels.
Main Results:
- MUS81 shows limited compensation for MutLγ loss and is not the sole alternative resolvase.
- Crossover interference persists but is weakened in mlh1 mutants, which exhibit reduced crossovers and increased aneuploidy.
- Loss of MutLγ can be suppressed by eliminating FANCM, suggesting resolution by DNA helicases/Top3α complexes.
- Elevated MLH1/MLH3 expression increases crossovers, while misregulation severely reduces them and plant fertility.
- PMS1, a MutLα component, is not involved in crossing over.
Conclusions:
- MutLγ plays a unique and essential role in regulating ZMM-dependent meiotic crossovers.
- Alternative resolution pathways involving DNA helicases exist but are insufficient without MutLγ.
- Precise control of MLH1/MLH3 levels is critical for maintaining crossover numbers, genome stability, and fertility.
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