Homologous chromosomes are stably conjoined for Drosophila male meiosis I by SUM, a multimerized protein assembly with modules for DNA-binding and for separase-mediated dissociation co-opted from cohesin.

Autor: Kabakci Z; Department of Molecular Life Science (DMLS), University of Zurich, Zurich, Switzerland., Reichle HE; Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany., Lemke B; Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany., Rousova D; Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany., Gupta S; Department of Molecular Life Science (DMLS), University of Zurich, Zurich, Switzerland., Weber J; Department of Molecular Life Science (DMLS), University of Zurich, Zurich, Switzerland., Schleiffer A; Research Institute of Molecular Pathology (IMP), Vienna BioCenter, Vienna, Austria., Weir JR; Friedrich Miescher Laboratory of the Max Planck Society, Tübingen, Germany., Lehner CF; Department of Molecular Life Science (DMLS), University of Zurich, Zurich, Switzerland.
Jazyk: angličtina
Zdroj: PLoS genetics [PLoS Genet] 2022 Dec 08; Vol. 18 (12), pp. e1010547. Date of Electronic Publication: 2022 Dec 08 (Print Publication: 2022).
DOI: 10.1371/journal.pgen.1010547
Abstrakt: For meiosis I, homologous chromosomes must be paired into bivalents. Maintenance of homolog conjunction in bivalents until anaphase I depends on crossovers in canonical meiosis. However, instead of crossovers, an alternative system achieves homolog conjunction during the achiasmate male meiosis of Drosophila melanogaster. The proteins SNM, UNO and MNM are likely constituents of a physical linkage that conjoins homologs in D. melanogaster spermatocytes. Here, we report that SNM binds tightly to the C-terminal region of UNO. This interaction is homologous to that of the cohesin subunits stromalin/Scc3/STAG and α-kleisin, as revealed by sequence similarities, structure modeling and cross-link mass spectrometry. Importantly, purified SU_C, the heterodimeric complex of SNM and the C-terminal region of UNO, displayed DNA-binding in vitro. DNA-binding was severely impaired by mutational elimination of positively charged residues from the C-terminal helix of UNO. Phenotypic analyses in flies fully confirmed the physiological relevance of this basic helix for chromosome-binding and homolog conjunction during male meiosis. Beyond DNA, SU_C also bound MNM, one of many isoforms expressed from the complex mod(mdg4) locus. This binding of MNM to SU_C was mediated by the MNM-specific C-terminal region, while the purified N-terminal part common to all Mod(mdg4) isoforms multimerized into hexamers in vitro. Similarly, the UNO N-terminal domain formed tetramers in vitro. Thus, we suggest that multimerization confers to SUM, the assemblies composed of SNM, UNO and MNM, the capacity to conjoin homologous chromosomes stably by the resultant multivalent DNA-binding. Moreover, to permit homolog separation during anaphase I, SUM is dissociated by separase, since UNO, the α-kleisin-related protein, includes a separase cleavage site. In support of this proposal, we demonstrate that UNO cleavage by tobacco etch virus protease is sufficient to release homolog conjunction in vivo after mutational exchange of the separase cleavage site with that of the bio-orthogonal protease.
Competing Interests: The authors have declared that no competing interests exist.
(Copyright: © 2022 Kabakci et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
Databáze: MEDLINE
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