Abstract
The American Cancer Society’s 2009 statistics estimate that 1 out of every 4 deaths is cancer related. Genomic instability is a common feature of cancerous states, and an increase in genomic instability is the diagnostic feature of Bloom Syndrome. Bloom Syndrome, a rare disorder characterized by a predisposition to cancer, is caused by mutations of the BLM gene. This study focuses on the partnerships of BLM protein to RAD51, a Homologous Recombination repair protein essential for survival. A systematic set of BLM deletion fragments were generated to refine the protein binding domains of BLM to RAD51 and determine interacting regions of BLM and ssDNA. Results show that RAD51 and ssDNA interact in overlapping regions; BLM100–214 and BLM1317–1367. The overlapping nature of these regions suggests a preferential binding for one partner that could function to regulate homologous recombination and therefore helps to clarify the role of BLM in maintaining genomic stability.
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Abbreviations
- HR:
-
Homologous recombination
- DSB:
-
DNA double-strand breaks
- SDSA:
-
Synthesis-dependent strand annealing
- BIR:
-
Break induced replication
- DHJ:
-
Double holliday junction
- BS:
-
Bloom syndrome
- SCE:
-
Sister chromatid exchange
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Acknowledgments
The authors thank Drs. Susan A. Gerbi and Robert W. Sobol, for their helpful discussions and critical reading of this manuscript. We also thank Dr. Nathan Ellis for his kind gift of BLM cDNA. This work was supported by the RI-INBRE Grant #P20 RR16457 from National Center for Research Resources/National Institutes of Health to KHA.
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Bergeron, K.L., Murphy, E.L., Brown, L.W. et al. Critical Interaction Domains between Bloom Syndrome Protein and RAD51. Protein J 30, 1–8 (2011). https://doi.org/10.1007/s10930-010-9295-8
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DOI: https://doi.org/10.1007/s10930-010-9295-8