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Updated: May 8, 2026

Quantitation and Analysis of the Formation of HO-Endonuclease Stimulated Chromosomal Translocations by Single-Strand Annealing in Saccharomyces cerevisiae
09:40

Quantitation and Analysis of the Formation of HO-Endonuclease Stimulated Chromosomal Translocations by Single-Strand Annealing in Saccharomyces cerevisiae

Published on: September 23, 2011

Spt2p defines a new transcription-dependent gross chromosomal rearrangement pathway

Nilabja Sikdar1, Soma Banerjee, Han Zhang

  • 1Genome Instability Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America.

Plos Genetics
|December 6, 2008
PubMed

Insights

High mobility group 1 (HMG1) protein overexpression, similar to Spt2p in yeast, increases gross chromosomal rearrangements (GCRs). This occurs via increased single-stranded DNA during transcription, leading to genomic instability.

Area of Science:

  • Genetics
  • Molecular Biology
  • Cancer Research

Background:

  • Gross chromosomal rearrangements (GCRs) are common in cancers.
  • High mobility group 1 (HMG1) protein is upregulated in tumors and may induce GCRs by altering DNA structure.

Purpose of the Study:

  • To investigate the role of Spt2p, a yeast homolog of HMG1, in GCR formation.
  • To elucidate the mechanism by which Spt2p influences genomic instability.

Main Methods:

  • Overexpression of Spt2p in Saccharomyces cerevisiae.
  • Assessing GCRs in relation to transcription elongation and polyadenylation.
  • Measuring cell cycle progression and single-stranded DNA (ssDNA) levels.
  • Evaluating the effect of RNase H expression on GCRs.
  • Analyzing GCR formation at specific chromosomal locations.

Main Results:

  • Spt2p overexpression enhanced GCRs, dependent on transcription and polyadenylation factors.
  • Excess Spt2p led to increased S phase cells and ssDNA, potentially causing DNA damage.
  • RNase H expression reduced GCRs in Spt2p-overexpressing cells.
  • High transcription levels correlated with increased GCR formation.

Conclusions:

  • Spt2p acts as a novel pathway contributing to GCRs.
  • Increased ssDNA during transcription elongation is a key factor in Spt2p-mediated genomic instability.
  • Transcription-associated DNA intermediates can drive genomic instability.

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