DNA (‘the Blueprint of Life’) must be reproduced, interpreted and modified by cells to ensure survival. In simple terms, DNA interactions can be accomplished in two ways. One DNA molecule (a chromosome) can become tethered to another DNA molecule. A prime example occurs during DNA replication. Each chromosome is duplicated and the resulting sister chromatids (the products of chromosome replication) become tethered together. Evidence obtained by the Skibbens lab and others suggest that the process of tethering together sister chromatids is coordinated with DNA replication fork and occurs in proximity to other forms of DNA chromatinizations that include histone deposition and condensin recruitment (Images modified from Rudra and Skibbens 2013 J Cell Science).
A second type of DNA interaction occurs when a chromosome loops back on itself to stabilize the assembly of protein complexes at that intersection. An example here is transcription regulation – different sequences of DNA such as enhancers and promoters must come into registration to facilitate the assembly of protein complexes through which DNA is transcribed into RNA. Enhancers and promoters, however, often reside on a chromosome at large distances from one another. DNA looping allows these DNA sequences (E=Enhancer, P=Promoter) to come into close proximity with the base of these loops similarly tethered together by cohesins (Red). Note that looping is also critical for chromosome condensation, a process through which long, amorphous strands of DNA become compacted into discrete structures (Images modified from Skibbens 2015 Current Biology).
Cohesins are a complex of proteins that stabilize all sorts of DNA-DNA interactions including sister-sister chromatid tethering, enhance-promoter registration and even associations of non-identical DNA sequences across different chromosomes. As such, cohesins are essential for chromosome segregation, transcription regulation and DNA repair. Ctf7/Eco1 (and human homologs ESCO1 and ESCO2) is an essential regulator of cohesins of tremendous clinical importance. For instance, mutations in ESCO family members are associated with aneuploidy (hallmark of cancer cells), cell death and severe developmental defects which likely arise through deregulation of transcription programs required for proper development (Image modified from Skibbens 2015 Current Biology).
The Skibbens Lab actively pursues all aspects of cohesin and ESCO-type protein functions. While we predominantly use yeast as a model system, collaborations with the Cassimeris and Iovine labs using human tissue culture cells and zebrafish fin regeneration, respectively providing exciting insights into defects that in humans lead to severe disease states including cancer and birth defects.
Research Funding
Completed Awards
Competitively awarded research grants
National Institute of General Medicine Sciences Grant, 2022-2024
Department of Health and Human Services
Principal Investigator: Robert V. Skibbens
"Novel targets of CRL4 ligase within Cohesinopathy pathways"
Award No. 1R03HD107169-01
National Institute of General Medicine Sciences Grant, 2020-2023
Department of Health and Human Services
Principal Investigator: Robert V. Skibbens
"Novel targets of the Roberts Syndrome acetyltransferase Esco2/Eco1"
Award No. 1R15GM139097-01
National Institute of General Medicine Sciences Grant, 2014-2020
Department of Health and Human Services
Principal Investigator: Robert V. Skibbens
"DNA helicase and replication factor functions in genome maintenance"
Award No. 1R15GM110631-01
National Institute of General Medical Sciences Grant, 2011-2014
Department of Health and Human Services
Principal Investigator – Robert V. Skibbens
“Mechanisms of sister chromatid pairing”
Award No. 1R15GM083269-02
Susan G. Komen for the Cure Research Grant, 2007-2010
Basic, Clinical and Translational Research - Division of Tumor Cell Biology
Principal Investigator – Robert V. Skibbens
“Cohesion-dependent Mechanisms of Cancer Progression and Aneuploidy”
Award No. BCTR0707708
National Institute of General Medical Sciences Grant, 2008-2010
Department of Health and Human Services
Principal Investigator – Robert V. Skibbens
“Mechanisms of sister chromatid pairing”
Award No. 1R15GM083269-01
National Sciences Foundation Research Grant, 2002-2005
Division of Eukaryotic Genetics
Principal Investigator – Robert V. Skibbens
“Mechanisms of Sister Chromatid Pairing”
Award No. MCB-0212323