DNA helicases Sgs1 and BLM promote DNA double-strand break resection.
By S. Gravel, J. R. Chapman, C. Magill, Stephen P. Jackson. Genes & Development, 2008
601 citations recorded by the source corpus.
A key cellular response to DNA double-strand breaks (DSBs) is 5'-to-3' DSB resection by nucleases to generate regions of ssDNA that then trigger cell cycle checkpoint signaling and DSB repair by homologous recombination (HR). Here, we reveal that in the absence of exonuclease Exo1 activity, deletion or mutation of the Saccharomyces cerevisiae RecQ-family helicase, Sgs1, causes pronounced hypersensitivity to DSB-inducing agents. Moreover, we establish that this reflects severely compromised DSB resection, deficient DNA damage signaling, and strongly impaired HR-mediated repair. Furthermore, we show that the mammalian Sgs1 ortholog, BLM--whose deficiency causes cancer predisposition and infertility in people--also functions in parallel with Exo1 to promote DSB resection, DSB signaling and resistance to DSB-generating agents. Collectively, these data establish evolutionarily conserved roles for the BLM and Sgs1 helicases in DSB processing, signaling, and repair.
Subfields: Cancer Research, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/58c81dfd7876dcb6a0eebba3ccbfd1c9d33fc81a
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Citations in the corpus
- Regulation of homologous recombination in eukaryotes (2010, background): “Biochemical and genetic evidence demonstrate an involvement of the RecQ helicases Sgs1 (yeast) and BLM (human) in DSB resection (62, 103, 114, 173) besides functions in joint reversal, dHJ dissolution, and in DDR signaling (15).”
- Repair Pathway Choices and Consequences at the Double-Strand Break (2015, unknown): “Two recent studies uncovered a dual role for BLM in DSB repair: BLM can repress alt-EJ in a manner epistatic with 53BP1 and Rif1; conversely, in the absence of 53BP1 or Rif1, BLM can also favor alt-EJ [59,60].”