Background: The Saccharomyces cerevisiae RecQ helicase Sgs1 is essential for mitotic and meiotic genome stability. The stage at which Sgs1 acts during meiosis is subject to debate. Cytological experiments showed that a deletion of SGS1 leads to an increase in synapsis initiation complexes and axial associations leading to the proposal that it has an early role in unwinding surplus strand invasion events. Physical studies of recombination intermediates implicate it in the dissolution of double Holliday junctions between sister chromatids.
Methodology/principal Findings: In this work, we observed an increase in meiotic recombination between diverged sequences (homeologous recombination) and an increase in unequal sister chromatid events when SGS1 is deleted. The first of these observations is most consistent with an early role of Sgs1 in unwinding inappropriate strand invasion events while the second is consistent with unwinding or dissolution of recombination intermediates in an Mlh1- and Top3-dependent manner. We also provide data that suggest that Sgs1 is involved in the rejection of 'second strand capture' when sequence divergence is present. Finally, we have identified a novel class of tetrads where non-sister spores (pairs of spores where each contains a centromere marker from a different parent) are inviable. We propose a model for this unusual pattern of viability based on the inability of sgs1 mutants to untangle intertwined chromosomes. Our data suggest that this role of Sgs1 is not dependent on its interaction with Top3. We propose that in the absence of SGS1 chromosomes may sometimes remain entangled at the end of pre-meiotic replication. This, combined with reciprocal crossing over, could lead to physical destruction of the recombined and entangled chromosomes. We hypothesise that Sgs1, acting in concert with the topoisomerase Top2, resolves these structures.
Conclusions: This work provides evidence that Sgs1 interacts with various partner proteins to maintain genome stability throughout meiosis.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976770 | PMC |
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0015380 | PLOS |
J Biochem Mol Toxicol
December 2024
Genome Stability Regulation Lab, School of Biotechnology, Shri Mata Vaishno Devi University, Katra, Jammu & Kashmir, India.
Ucc1, an F-box motif-containing protein of Saccharomyces cerevisiae encoded by UCC1 regulates energy metabolism through proteasomal degradation of citrate synthase Cit2 and inactivation of the glyoxylate cycle when glucose is present as the main carbon source in the growth medium. Rrm3, a Pif1 family DNA helicase, encoded by RRM3 regulates the movement of the replication forks during the DNA replication process. Here in this study, we present evidence of binary genetic interaction between both the genes, UCC1 and RRM3, that determine the growth rate, cell morphology, cell size, apoptosis, and stress response.
View Article and Find Full Text PDFbioRxiv
September 2024
Howard Hughes Medical Institute, University of California Davis, Davis, CA, USA.
Chromosomal linkages formed through crossover recombination are essential for accurate segregation of homologous chromosomes during meiosis. DNA events of recombination are spatially and functionally linked to structural components of meiotic chromosomes. Imperatively, biased resolution of double-Holliday junction (dHJ) intermediates into crossovers occurs within the synaptonemal complex (SC), the meiosis-specific structure that mediates homolog synapsis during the pachytene stage.
View Article and Find Full Text PDFMalar J
August 2024
Evolutionary Ecology and Infection biology, Department of Biology, Lund University, Lund, Sweden.
Stalled replication forks can be processed by several distinct mechanisms collectively called post-replication repair which includes homologous recombination, fork regression, and translesion DNA synthesis. However, the regulation of the usage between these pathways is not fully understood. The Rad51 protein plays a pivotal role in maintaining genomic stability through its roles in HR and in protecting stalled replication forks from degradation.
View Article and Find Full Text PDFEMBO J
July 2024
Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
The Mec1/ATR kinase is crucial for genome stability, yet the mechanism by which it prevents gross chromosomal rearrangements (GCRs) remains unknown. Here we find that in cells with deficient Mec1 signaling, GCRs accumulate due to the deregulation of multiple steps in homologous recombination (HR). Mec1 primarily suppresses GCRs through its role in activating the canonical checkpoint kinase Rad53, which ensures the proper control of DNA end resection.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!