Role of Deubiquitination in Fanconi Anemia Cancer Susceptibility Pathway View Homepage


Ontology type: schema:MonetaryGrant     


Grant Info

YEARS

2009-2015

FUNDING AMOUNT

2277736 USD

ABSTRACT

DESCRIPTION (provided by applicant): Inherited or acquired deficiencies in genome stability pathways are known to cause a variety of human pathological conditions, including early onset cancer. The familial genome instability or cancer susceptibility syndrome, Fanconi Anemia (FA), is caused by mutations in 1 of at least 13 FA genes. Biallelic mutations in some of these genes also occur in cancers of non-FA patients, implicating these genes in tumor suppression or genome maintenance among the general population. These genes act in a common molecular pathway that modulates DNA repair, especially the repair of DNA interstrand cross-links. Protein ubiquitination and deubiquitination are dynamic processes implicated in the regulation of numerous cellular pathways. Monoubiquitination of the FA protein FANCD2 appears to be critical in the repair of DNA damage because many of the proteins that are mutated in FA are required for FANCD2 ubiquitination. By screening a gene family RNAi library, we identified a deubiquitinating enzyme as a novel component of the FA pathway. Despite the number of recent studies that have helped identify key players for the activation of the FA pathway, it is still unclear how the regulation of the FA pathway is achieved. The research conducted in my laboratory is directed towards understanding the delicate balance between the positive and negative regulators of ubiquitination in the FA pathway. The proposed research concerns enzymes of the ubiquitin system controlling DNA repair and genome stability. Accumulating evidence indicates that defects in the DNA damage response can lead to cancer initiation. The results of our studies will help to define the molecular mechanisms of the Fanconi Anemia pathway and how dysregulation of this pathway can lead to oncogenesis. More... »

URL

http://projectreporter.nih.gov/project_info_description.cfm?aid=8403008

Related SciGraph Publications

  • 2012-12. The Fanconi anemia pathway in replication stress and DNA crosslink repair in CELLULAR AND MOLECULAR LIFE SCIENCES
  • 2007-06. FANCI is a second monoubiquitinated member of the Fanconi anemia pathway in NATURE STRUCTURAL & MOLECULAR BIOLOGY
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