Interdisciplinary Graduate Program
Program in Molecular Medicine
First Thesis Advisor
William Theurkauf, PhD
Caenorhabditis elegans, Chromatin, Chromosome Segregation, Genetic Dosage Compensation, Adenosine Triphosphatases, DNA-Binding Proteins
Dissertations, UMMS; Caenorhabditis elegans; Chromatin; Chromosome Segregation; Dosage Compensation, Genetic; Adenosine Triphosphatases; DNA-Binding Proteins
Chromatin is organized dynamically to accommodate different biological processes. One of the factors required for proper chromatin organization is a group of complexes called condensins. Most eukaryotes have two conserved condensins (I and II) required for chromosome segregation. C. elegans has a third condensin (IDC) that specializes in dosage compensation, a process that down-regulates X gene dosage in XX hermaphrodites to match the dosage in XO males. How the three condensins are regulated is not well understood. Here, I present the discovery and characterization of a novel condensin regulator, SMCL-1.
We identified SMCL-1 through purification of a MAP-tagged condensin subunit. Condensins are comprised of SMC ATPases and regulatory CAP proteins; SMCL-1 interacts most abundantly with condensin SMC subunits and resembles the ATPase domain of SMC proteins. Interestingly, the SMCL-1 protein has residues that differ from SMC consensus and potentially render SMCL-1 incapable of hydrolyzing ATP. Worms harboring smcl-1 deletion are viable and show no detectable phenotype. However, deleting smcl-1 in a condensin hypomorph mildly suppresses condensin I and IDC mutant phenotypes, suggesting that SMCL-1 functions as a negative regulator of condensin I and IDC. Consistent with this, overexpression of SMCL-1 leads to condensin loss-of-function phenotypes such as lethality, segregation defects and disruption of IDC localization on the X chromosomes. Homology searches based on the unique ATPase domain of SMCL-1 reveal that SMCL-1-like proteins are present only in organisms also predicted to have condensin IDC. Taken together, we conclude that SMCL-1 is a negative modulator of condensin functions and we propose a role for SMCL-1 in helping organisms adapt to having a third condensin by maintaining the balance among three condensin complexes.
Chao, LF. A Novel SMC-Like Protein Modulates C. Elegans Condensin Functions: A Dissertation. (2016). University of Massachusetts Medical School. GSBS Dissertations and Theses. Paper 820. DOI: 10.13028/M2V018. https://escholarship.umassmed.edu/gsbs_diss/820
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