Biochemical Approach to Understanding the Fanconi Anemia Pathway- Regulated Nucleases in Genome Maintenance for Preventing Bone Marrow Failure and Cancer

摘要

Fanconi anemia is the most prevalent inherited BMF syndromes, caused by mutations in at least 16 genes. A hallmark of FA is cellular hypersensitivity to agents that form interstrand cross-links (ICLs). The FA pathway maintains genome stability by coordinating the necessary repair response required for the full removal of ICLs. However, the specific function of FA proteins and associated factor remain a very important puzzle to solve. Failed or inappropriate attempts to repair ICL lesions will result in genomic instability that has been postulated to be the genetic causes of both BMF and subsequent cancer development in FA patients. The objective of the proposed project is to develop biochemical systems to characterize the molecular details of ICL repair involved in genome maintenance. Comprehension in such molecular mechanisms will contribute to elucidating both the cause for initiation and step-wise transformation of BMF syndromes to cancer.