The HORMA domain: an evolutionarily conserved domain discovered in chromatin-associated proteins, has unanticipated diverse functions

Muniyappa, K.; Kshirsagar, Rucha; Ghodke, Indrajeet

doi:10.1016/j.gene.2014.05.020

Cited by 19 publications

(11 citation statements)

References 38 publications

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“…Therefore, we reasoned that the phosphorylation of ASY1 may control its interaction with ASY3. The first 300 amino acids of ASY1 (ASY1 1-300 ), which include the HORMA domain, essential for the protein-protein interaction of Hop1 with Red1 (Muniyappa et al, 2014;Rosenberg & Corbett, 2015), were found to interact with ASY3 in a yeast two-hybrid assay consistent with earlier results (Ferdous et al, 2012). While no obvious effect of ASY1 1-300/T184V on the interaction capacities with ASY3 was observed, we found that the binding of ASY1 1-300/T142V to ASY3 was strongly decreased, yet not fully abolished, since yeast cells harboring ASY1 1-300/T142V and ASY3 cannot grow on the stringent selection media (without histidine and adenine) but do survive on the less stringent media (without histidine; Fig 4A).…”

Section: Phosphorylation Of Asy1 Increases Its Binding Affinity With supporting

confidence: 87%

The Arabidopsis Cdk1/Cdk2 homolog CDKA ;1 controls chromosome axis assembly during plant meiosis

et al. 2019

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Meiosis is key to sexual reproduction and genetic diversity. Here, we show that the Arabidopsis cyclin‐dependent kinase Cdk1/Cdk2 homolog CDKA;1 is an important regulator of meiosis needed for several aspects of meiosis such as chromosome synapsis. We identify the chromosome axis protein ASYNAPTIC 1 (ASY1), the Arabidopsis homolog of Hop1 (homolog pairing 1), essential for synaptonemal complex formation, as a target of CDKA;1. The phosphorylation of ASY1 is required for its recruitment to the chromosome axis via ASYNAPTIC 3 (ASY3), the Arabidopsis reductional division 1 (Red1) homolog, counteracting the disassembly activity of the AAA+ ATPase PACHYTENE CHECKPOINT 2 (PCH2). Furthermore, we have identified the closure motif in ASY1, typical for HORMA domain proteins, and provide evidence that the phosphorylation of ASY1 regulates the putative self‐polymerization of ASY1 along the chromosome axis. Hence, the phosphorylation of ASY1 by CDKA;1 appears to be a two‐pronged mechanism to initiate chromosome axis formation in meiosis.

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Section: Phosphorylation Of Asy1 Increases Its Binding Affinity With supporting

confidence: 87%

The Arabidopsis Cdk1/Cdk2 homolog CDKA ;1 controls chromosome axis assembly during plant meiosis

et al. 2019

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“…First, considering that the N-terminal HORMA domain (15-228 amino acid for ASY1) is well-known to function as an intact unit ( 15 , 30 , 31 ), we wondered whether an additional short deletion at the N-terminus of ASY1 Δ10 :GFP would disrupt the interaction of the HORMA domain with the closure motif and thus, recover its nuclear localization in the wild-type background. To test this, we created a version of ASY1 missing the first 2–20 aa ( PRO ASY1 :ASY1 Δ2-20 :GFP , called ASY1 Δ20 :GFP ) (Figure 1A ).…”

Section: Resultsmentioning

confidence: 99%

State changes of the HORMA protein ASY1 are mediated by an interplay between its closure motif and PCH2

Yang

Portheine

et al. 2020

Nucleic Acids Research

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HORMA domain-containing proteins (HORMADs) play an essential role in meiosis in many organisms. The meiotic HORMADs, including yeast Hop1, mouse HORMAD1 and HORMAD2, and Arabidopsis ASY1, assemble along chromosomes at early prophase and the closure motif at their C-termini has been hypothesized to be instrumental for this step by promoting HORMAD oligomerization. In late prophase, ASY1 and its homologs are progressively removed from synapsed chromosomes promoting chromosome synapsis and recombination. The conserved AAA+ ATPase PCH2/TRIP13 has been intensively studied for its role in removing HORMADs from synapsed chromosomes. In contrast, not much is known about how HORMADs are loaded onto chromosomes. Here, we reveal that the PCH2-mediated dissociation of the HORMA domain of ASY1 from its closure motif is important for the nuclear targeting and subsequent chromosomal loading of ASY1. This indicates that the promotion of ASY1 to an ‘unlocked’ state is a prerequisite for its nuclear localization and chromosomal assembly. Likewise, we find that the closure motif is also necessary for the removal of ASY1 by PCH2 later in prophase. Our work results in a unified new model for PCH2 and HORMADs function in meiosis and suggests a mechanism to contribute to unidirectionality in meiosis.

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“…Mad2 lacks those domains but does contain a HORMA domain, which is found in several chromatin-associated proteins (Aravind and Koonin 1998;Muniyappa et al 2014). To test whether Mad2 can bind directly to histones, we performed pull-down experiments using recombinant GST-yMad2 fusion proteins and calf thymus histones.…”

Section: Loss Of H3k4 Methylation Results In Benomyl Resistance and Amentioning

confidence: 99%

Histone H3K4 methylation regulates deactivation of the spindle assembly checkpoint through direct binding of Mad2

et al. 2016

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Histone H3 methylation on Lys4 (H3K4me) is associated with active gene transcription in all eukaryotes. In Saccharomyces cerevisiae, Set1 is the sole lysine methyltransferase required for mono-, di-, and trimethylation of this site. Although H3K4me3 is linked to gene expression, whether H3K4 methylation regulates other cellular processes, such as mitosis, is less clear. Here we show that both Set1 and H3K4 mutants display a benomyl resistance phenotype that requires components of the spindle assembly checkpoint (SAC), including Bub3 and Mad2. These proteins inhibit Cdc20, an activator of the anaphase-promoting complex/cyclosome (APC/C). Mutations in Cdc20 that block Mad2 interactions suppress the benomyl resistance of both set1 and H3K4 mutant cells. Furthermore, the HORMA domain in Mad2 directly binds H3, identifying a new histone H3 "reader" motif. Mad2 undergoes a conformational change important for execution of the SAC. We found that the closed (active) conformation of both yeast and human Mad2 is capable of binding methylated H3K4, but, in contrast, the open (inactive) Mad2 conformation limits interaction with methylated H3. Collectively, our data indicate that interactions between Mad2 and H3K4 regulate resolution of the SAC by limiting closed Mad2 availability for Cdc20 inhibition.

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The HORMA domain: an evolutionarily conserved domain discovered in chromatin-associated proteins, has unanticipated diverse functions

Cited by 19 publications

References 38 publications

The Arabidopsis Cdk1/Cdk2 homolog CDKA ;1 controls chromosome axis assembly during plant meiosis

The Arabidopsis Cdk1/Cdk2 homolog CDKA ;1 controls chromosome axis assembly during plant meiosis

State changes of the HORMA protein ASY1 are mediated by an interplay between its closure motif and PCH2

Histone H3K4 methylation regulates deactivation of the spindle assembly checkpoint through direct binding of Mad2

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