A Novel SMC-Like Protein Modulates C. Elegans Condensin Functions: A Dissertation
Authors
Chao, Lucy F.Faculty Advisor
William Theurkauf, PhDAcademic Program
Interdisciplinary Graduate ProgramUMass Chan Affiliations
Program in Molecular MedicineDocument Type
Doctoral DissertationPublication Date
2016-03-25Keywords
Dissertations, UMMSCaenorhabditis elegans
Chromatin
Chromosome Segregation
Dosage Compensation, Genetic
Adenosine Triphosphatases
DNA-Binding Proteins
Caenorhabditis elegans
Chromatin
Chromosome Segregation
Genetic Dosage Compensation
Adenosine Triphosphatases
DNA-Binding Proteins
Biochemistry, Biophysics, and Structural Biology
Genetics and Genomics
Metadata
Show full item recordAbstract
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.DOI
10.13028/M2V018Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32191Rights
Copyright is held by the author, with all rights reserved.ae974a485f413a2113503eed53cd6c53
10.13028/M2V018