In my lab, we study the manner in which cells control the key events of cell division. When cells divide, either in order to develop new tissues or to replace aging or defective cells, a precise and highly complex series of cellular events must be carefully coordinated. This coordination ensures that newly forming cells inherit the appropriate components and thus are able to function properly. In the course of experiments developed to better understand the control of cell division, we have identified a novel gene that is necessary to ensure accurate chromosome segregation to newly forming cells. Because the chromosomes carry essentially all genetic information within a cell, their accurate segregation during cell division is critical. In addition, errors in chromosome segregation are known to play an important role in the development of tumors, making a better understanding of this process a very worthy endeavor. Our lab uses several approaches to understand further the regulation of chromosome segregation. These include biochemical analyses using extracts from eggs of the frog Xenopus laevis and time-lapse image analysis of cultured cells.
Work in the Rankin lab is focused on understanding the chromosome cohesion apparatus, how it is regulated during cell division, and how aberrant cohesion contributes to disease. Although the essential mechanisms of cohesion are conserved throughout eukaryotic phylogeny, we are particularly interested in the metazoan elaborations of this system. Aberrant cohesion causes developmental defects and is associated with tumor progression.
The cohesin complex was discovered and initially characterized based on its role in tethering newly replicated copies of chromosomes together from the time they are made until cell division. This cohesion ensures accurate chromosome alignment and segregation in mitosis. Sister chromatid cohesion also supports DNA repair mechanisms that rely on homologous recombination.
In higher eukaryotes, cohesin also plays a critical role promoting normal chromosome structure. Cohesin ensures that chromosomes are packaged into loops and domains. This folding both compacts chromosomes and serves to define the transcriptional landscape. Cohesin in this role is thus a critical epigenetic regulator. Cohesinopathies, developmental disorders in individuals with compromised cohesin loading or function, are thought to reflect abnormal gene expression due to changes in chromosome structure.
My interest in cohesin regulation began a number of years ago with my discovery of the essential cohesin regulator Sororin. This activity is not present in fungal systems, which were the basis for our understanding of cohesin regulation at the time. We continue to work on Sororin, and have expanded the scope of study to include other cohesin regulators that are unique to or different in metazoans. We are particularly interested in how chromosome structure can be modulated to respond to DNA damage, to accommodate new transcriptional demands during development, and to promote orderly gene rearrangements in specific cells and tissues.
B.A., Reed College, Portland, OR, 1985
Ph.D., Tufts University School of Medicine, Boston, MA, 1995
Honors and Awards
1993-1994 Mortimer Sackler Scholar, Tufts University
1995-1998 Post-doctoral Fellow, Jane Coffin Childs Fund for Biomedical Research
1998-2000 Post-doctoral Fellow, Charles A. King Trust Medical Foundation
2008 Pew Foundation Scholar in Biomedical Research
Joined OMRF Scientific Staff in 2006.
da Silva EML, Rankin S. Chromosome Cohesion and Condensation in Xenopus Egg Extracts. Cold Spring Harb Protoc. 2018 Feb 23. [Epub ahead of print] PMID: 29475994
Alomer RM, da Silva EML, Chen J, Piekarz KM, McDonald K, Sansam CG, Sansam CL, Rankin S. Esco1 and Esco2 regulate distinct cohesin functions during cell cycle progression. Proc Natl Acad Sci USA. 2017 Sep 12;114(37):9906-11. PMCID: PMC5604028
Jordan PW, Eyster C, Chen J, Pezza RJ, Rankin S. Sororin is enriched at the central region of synapsed meiotic chromosomes. Chromosome Res. 2017 Jun;25(2):115-28. PMCID:PMC5441961
Sivakumar S, Daum JR, Tipton AR, Rankin S, Gorbsky GJ. The Spindle and kinetochore-associated (Ska) complex enhances binding of the Anaphase-Promoting Complex/Cyclosome (APC/C) to chromosomes and promotes mitotic exit. Mol Biol Cell 25:594-605, 2014. [Abstract]
Ouyang Z, Zheng G, Song J, Borek DM, Otwinowski Z, Brautigam CA, Tomchick DR, Rankin S, Yu H. Structure of the human cohesin inhibitor Wapl. Proc Natl Acad Sci U S A 110:11355-11360, 2013. [Abstract]
Daum JR, Potapova TA, Sivakumar S, Daniel JJ, Flynn JN, Rankin S, Gorbsky GJ. Cohesion fatigue induces chromatid separation in cells delayed at metaphase. Curr Biol 21:1018-1024, 2011. [Abstract]
Wu FM, Nguyen JV, Rankin S. A conserved motif at the C terminus of sororin is required for sister chromatid cohesion. J Biol Chem 286:3579-3586, 2011. [Abstract]
Lafont AL, Song J, Rankin S. Sororin cooperates with the acetyltransferase Eco2 to ensure DNA replication-dependent sister chromatid cohesion. Proc Natl Acad Sci U S A 107:20364-20369, 2010. [Abstract]
Rankin S, Ayad NG, Kirschner MW. Sororin, a substrate of the anaphase-promoting complex, is required for sister chromatid cohesion in vertebrates. Mol Cell 18:185-200, 2005. [Abstract]
Cell Cycle and Cancer Biology Research Program, MS 48
Oklahoma Medical Research Foundation
825 N.E. 13th Street
Oklahoma City, OK 73104
Phone: (405) 271-8190
Fax: (405) 271-7312