PgmNr Y467: The concerted function of the Shu complex and the Rad51 paralogs in Rad51 presynaptic assembly.

Authors:
K. A. Bernstein 1 ; T. McClendon 1 ; M. Sullivan 1 ; W. Gaines 2 ; S. K. Godin 1 ; P. Sung 2 ; J. Yanowitz 1 ; K. A. Bernstein 1


Institutes
1) Univ Pittsburgh School of Medicine, Pittsburgh, PA; 2) Yale University School of Medicine, New Haven, CT.


Keyword: 02. Chromosome structure, variation, evolution and dynamics

Abstract:

Double-strand breaks (DSBs) are one of the most cytotoxic forms of DNA damage.  Defects in DSB repair are associated with cancer predisposition, as well as, several heritable diseases including Fanconi anemia.  Our work has centered around Rad51 paralog function during DSB repair.  Importantly, mutations in the human Rad51 paralogs are found in tumors and also lead to Fanconi anemia.  Due to the embryonic lethality of the mouse knockout models and the low abundance and insolubility of the human proteins, there is very limited understanding as to how the Rad51 paralogs function to maintain genomic integrity. To circumvent these obstacles, we are studying the role of a unique Rad51 paralog-containing complex, called the Shu complex, in the budding yeast S. cerevisiae and the nematode C. elegans.  Although the Shu complex was discovered 10 years ago and is critical for DSB repair, its molecular function has remained elusive. We discovered that the yeast Shu complex is highly conserved from archaea through humans. Furthermore, we have identified direct physical interacting partners of the yeast and worm Shu complex and to show that these interactions are necessary and sufficient for the biological efficacy of the Shu complex during DSB repair.  We define a molecular role for the yeast and worm Shu complexes in Rad51 presynaptic filament assembly, and thus for the first time gained insight into its mechanistic function.  Our work has important implications for how the Rad51 paralogs and the human Shu complex function to prevent tumorigenesis and Fanconi anemia.



Yeast Database Genetic Index
1. gene symbol: RAD51; systematic name: YER095W
2. gene symbol: CSM2; systematic name: YIL132C
3. gene symbol: PSY3; systematic name: YLR376C
4. gene symbol: SHU1; systematic name: YHL006C
5. gene symbol: SHU2; systematic name: YDR078C