DNA single-strand break repair and spinocerebellar ataxia with axonal neuropathy-1.

Abstract

DNA single-strand breaks (SSBs) are the commonest DNA lesions arising spontaneously in cells, and if not repaired may block transcription or may be converted into potentially lethal/clastogenic DNA double-strand breaks (DSBs). Recently, evidence has emerged that defects in the rapid repair of SSBs preferentially impact the nervous system. In particular, spinocerebellar ataxia with axonal neuropathy (SCAN1) is a human disease that is associated with mutation of TDP1 (tyrosyl DNA phosphodiesterase 1) protein and with a defect in repairing certain types of SSBs. Although SCAN1 is a rare neurodegenerative disorder, understanding the molecular basis of this disease will lead to better understanding of neurodegenerative processes. Here we review recent progress in our understanding of TDP1, single-strand break repair (SSBR), and neurodegenerative disease.

• Authors: S F el-Khamisy, K W Caldecott
• Journal: Neuroscience (Neuroscience) Vol. 145 Issue 4 Pg. 1260-6 (Apr 14 2007) ISSN: 0306-4522 [Print] United States
• PMID: 17045754 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• DNA
• Phosphoric Diester Hydrolases
• TDP1 protein, human

Topics

• Animals
• Axons (metabolism, pathology)
• Cell Cycle (genetics)
• DNA (genetics)
• DNA Breaks, Single-Stranded
• DNA Repair (genetics)
• Genetic Predisposition to Disease (genetics)
• Humans
• Phosphoric Diester Hydrolases (genetics)
• Spinocerebellar Ataxias (genetics, metabolism, physiopathology)
• Wallerian Degeneration (genetics, metabolism, physiopathology)