Mirzaei H, et al. (2011) Sgs1 Truncations Induce Genome Rearrangements but Suppress Detrimental Effects of BLM Overexpression in Saccharomyces cerevisiae. J Mol Biol 405(4):877-91
Abstract: RecQ-like DNA helicases are conserved from bacteria to humans. They perform functions in the maintenance of genome stability, and their mutation is associated with cancer predisposition and premature aging syndromes in humans. Here, a series of C-terminal deletions and point mutations of Sgs1, the only RecQ-like helicase in yeast, show that the HRDC and Rad51 interaction domain are dispensable for Sgs1's role in suppressing genome instability, whereas the zinc-binding domain and the helicase domain are required. BLM expression from the native SGS1 promoter had no adverse effects on cell growth, but also was unable to complement any sgs1Delta defects. BLM overexpression, however, significantly increased the rate of accumulating GCRs in a dosage-dependent manner and greatly exacerbated sensitivity to DNA-damaging agents. Co-expressing sgs1 truncations of up to 900 residues, lacking all known functional domains of Sgs1, suppressed HU sensitivity of BLM overexpressing cells, suggesting a functional relationship between Sgs1 and BLM. Indeed, protein disorder prediction analysis of Sgs1 and BLM was used to produce a functional Sgs1-BLM chimera by replacing the N-terminus of BLM with the disordered N-terminus of Sgs1. The functionality of this chimera suggests that it is the disordered N-terminus, a site of protein binding and post-translational modification, that confers species-specificity to these two RecQ-like proteins.CI - Copyright (c) 2010. Published by Elsevier Ltd.
|Status: Published||Type: Journal Article||PubMed ID: 21111748|
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