Max Perutz Labs, Vienna Biocenter Campus (VBC), Vienna, Austria.
University of Vienna, Center for Molecular Biology, Department of Chromosome Biology, Vienna, Austria.
Nat Commun. 2024 Jun 3;15(1):4729. doi: 10.1038/s41467-024-49178-0.
Cohesin mediates sister chromatid cohesion to enable chromosome segregation and DNA damage repair. To perform these functions, cohesin needs to be protected from WAPL, which otherwise releases cohesin from DNA. It has been proposed that cohesin is protected from WAPL by SORORIN. However, in vivo evidence for this antagonism is missing and SORORIN is only known to exist in vertebrates and insects. It is therefore unknown how important and widespread SORORIN's functions are. Here we report the identification of SORORIN orthologs in Schizosaccharomyces pombe (Sor1) and Arabidopsis thaliana (AtSORORIN). sor1Δ mutants display cohesion defects, which are partially alleviated by wpl1Δ. Atsororin mutant plants display dwarfism, tissue specific cohesion defects and chromosome mis-segregation. Furthermore, Atsororin mutant plants are sterile and separate sister chromatids prematurely at anaphase I. The somatic, but not the meiotic deficiencies can be alleviated by loss of WAPL. These results provide in vivo evidence for SORORIN antagonizing WAPL, reveal that SORORIN is present in organisms beyond the animal kingdom and indicate that it has acquired tissue specific functions in plants.
黏连蛋白介导姐妹染色单体黏合,以实现染色体分离和 DNA 损伤修复。为了发挥这些功能,黏连蛋白需要免受 WAPL 的影响,否则 WAPL 会将黏连蛋白从 DNA 上释放下来。有观点认为,SORORIN 可以保护黏连蛋白免受 WAPL 的影响。然而,目前缺乏这种拮抗作用的体内证据,并且 SORORIN 仅存在于脊椎动物和昆虫中。因此,尚不清楚 SORORIN 的功能有多重要和广泛。在这里,我们在酿酒酵母(Sor1)和拟南芥(AtSORORIN)中鉴定了 SORORIN 的同源物。sor1Δ 突变体表现出黏合缺陷,这部分可被 wpl1Δ 缓解。Atsororin 突变体植物表现出矮化、组织特异性黏合缺陷和染色体错误分离。此外,Atsororin 突变体植物不育,在有丝分裂后期 I 过早分离姐妹染色单体。体细胞而非减数分裂的缺陷可以通过 WAPL 的缺失得到缓解。这些结果为 SORORIN 拮抗 WAPL 提供了体内证据,表明 SORORIN 存在于动物王国之外的生物体中,并表明它在植物中获得了组织特异性功能。