Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 100, Issue 19, Pages 10854-10859Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1934561100
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- NIGMS NIH HHS [R01 GM052319, GM52319] Funding Source: Medline
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Yeast strains with mutations in both TEL1 and MEC1 have short telomeres and elevated rates of chromosome deletions. By using a PCR assay, we demonstrate that mec1 tel1 strains also have telomere-telomere fusions (T-TFs). T-TFs require Lig4p (a ligase required for nonhomologous end-joining DNA repair). The highest rates of T-TFs are found in strains with combination of mutations that affect telomere length and DNA damage checkpoints (mec1 tel1, mec3 tel1, mrel1 mec1, and ddc1 tel1 strains). Examining many mutant genotypes, we find good agreement between the level of T-TFs and the rate of chromosomal deletions. In addition, if telomeres are elongated in a mec1 tel1 strain, we eliminate T-TFs and reduce the deletion rate. The correlation between the level of T-TFs and the rate of deletions argues that many of these deletions reflect a cycle of T-TF formation (resulting in dicentric chromosomes), followed by chromosome breakage.
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