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Abstract
Structural Maintenance of Chromosomes (SMC) family proteins participate in multisubunit complexes that govern chromosome structure and dynamics. SMC-containing condensin complexes create chromosome topologies essential for mitosis/meiosis, gene expression, recombination, and repair. Many eukaryotes have two condensin complexes (I and II); C. elegans has three (I, II, and the X-chromosome specialized condensin IDC) and their regulation is poorly understood. Here we identify a novel SMC-like protein, SMCL-1, that binds to C. elegans condensin SMC subunits, and modulates condensin functions. Consistent with a possible role as a negative regulator, loss of SMCL-1 partially rescued the lethal and sterile phenotypes of a hypomorphic condensin mutant, while over-expression of SMCL-1 caused lethality, chromosome mis-segregation, and disruption of condensin IDC localization on X chromosomes. Unlike canonical SMC proteins, SMCL-1 lacks hinge and coil domains, and its ATPase domain lacks conserved amino acids required for ATP hydrolysis, leading to the speculation that it may inhibit condensin ATPase activity. SMCL-1 homologs are apparent only in the subset of Caenorhabditis species in which the condensin I and II subunit SMC-4 duplicated to create the condensin IDC- specific subunit DPY-27, suggesting that SMCL-1 helps this lineage cope with the regulatory challenges imposed by evolution of a third condensin complex. Our findings uncover a new regulator of condensins and highlight how the duplication and divergence of SMC complex components in various lineages has created new proteins with diverse functions in chromosome dynamics.
Highlights
DPY-27 (IDC), DPY-26 (I & IDC) and KLE-2 (II) were each fused to the Multifunctional tandem Affinity Purification (MAP) tag that includes the fluorescent protein mVenus, the FLAG epitope, and the Streptavidin Binding Peptide (SBP) [46] (Fig 1B)
Tandem affinity purification from adult hermaphrodite extracts was performed (Fig 1B), co- purified proteins were identified by MudPIT mass spectrometry, and proteins identified in two replicates and not in an untagged wild-type control sample were ranked by their Normalized Spectral Abundance Factor (NSAF) values [47]
To test if the SMCL-1 overexpression lethality phenotype was due to disrupting condensin function, we reduced the heat-shock regimen to a single non-lethal induction and assayed its effect on two known condensin functions: chromosome segregation and dosage compensation
Summary
Condensins are conserved protein complexes that reconfigure chromosome architecture to promote chromosome segregation, recombination, DNA repair, and gene expression regulation (reviewed in [1,2,3,4,5]). Condensins drive ATP-dependent supercoiling, compaction, and entrapment of DNA strands [6]. Across the three domains of life, condensins compact and segregate chromosomes during cell division. Condensins organize chromosome topology during interphase and are implicated in a variety of organism- and cell type-specific aspects of chromosome function such as gene regulation. Consistent with diverse important roles in chromosome dynamics, loss of condensin function in vivo causes severe phenotypes and often lethality
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