Cohesin is a ring complex closed with structural maintenance of chromosome 1(SMC-1),SMC-3,and a kleisin subunit,mediating sister chromatid cohesion in mitosis and meiosis.Kleisin N-and C-terminal domains interact with...Cohesin is a ring complex closed with structural maintenance of chromosome 1(SMC-1),SMC-3,and a kleisin subunit,mediating sister chromatid cohesion in mitosis and meiosis.Kleisin N-and C-terminal domains interact with SMC-3 and SMC-1,forming two distinct cohesin gates.Whether these gates are specialized for mitosis and meiosis remains elusive.Here,we create Caenorhabditis elegans mutants that express chimeric proteins swapping N-and C-terminal domains between different kleisins to investigate how these gates are specialized for different cell division programs.Replacing the meiotic REC-8 N-terminus with that of a cell divisionunrelated kleisin COH-1 or the mitotic kleisin sister chromatid cohesion protein 1(SCC-1)disrupts inter-sister chromatid cohesion and causes severe meiotic defects.Swapping the REC-8 C-terminus with that of COH-1 or SCC-1 largely retains the meiotic functions of REC-8 but causes age-related chromosome abnormalities.A specialized C-terminus is also required for the functions of SCC-1.Furthermore,point mutations inthe REC-8C-terminus cause severe meiotic defects without impairing the SMC-1-kleisin interaction,suggesting an integrated SMC-1-kleisin gate.These findings suggest the requirements for specialized cohesin gates in different biological processes.展开更多
基金supported by grants from the National Natural Science Foundation of China(32022018 and32370780)the National Key Research and Development Program of China(2021YFA1101001)Some strains were provided by the Caenorhabditis Genetic Center(CGC),which is funded by National Institutes of Health(NIH)Office of Research Infrastructure Programs(P400D010440).
文摘Cohesin is a ring complex closed with structural maintenance of chromosome 1(SMC-1),SMC-3,and a kleisin subunit,mediating sister chromatid cohesion in mitosis and meiosis.Kleisin N-and C-terminal domains interact with SMC-3 and SMC-1,forming two distinct cohesin gates.Whether these gates are specialized for mitosis and meiosis remains elusive.Here,we create Caenorhabditis elegans mutants that express chimeric proteins swapping N-and C-terminal domains between different kleisins to investigate how these gates are specialized for different cell division programs.Replacing the meiotic REC-8 N-terminus with that of a cell divisionunrelated kleisin COH-1 or the mitotic kleisin sister chromatid cohesion protein 1(SCC-1)disrupts inter-sister chromatid cohesion and causes severe meiotic defects.Swapping the REC-8 C-terminus with that of COH-1 or SCC-1 largely retains the meiotic functions of REC-8 but causes age-related chromosome abnormalities.A specialized C-terminus is also required for the functions of SCC-1.Furthermore,point mutations inthe REC-8C-terminus cause severe meiotic defects without impairing the SMC-1-kleisin interaction,suggesting an integrated SMC-1-kleisin gate.These findings suggest the requirements for specialized cohesin gates in different biological processes.
