Publication

Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats

Warmerdam, D. O., van den Berg, J. & Medema, R. H., 22-Mar-2016, In : Cell reports. 14, 11, p. 2519-2527 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Daniel O. Warmerdam
  • Jeroen van den Berg
  • Rene H. Medema

rDNA repeats constitute the most heavily transcribed region in the human genome. Tumors frequently display elevated levels of recombination in rDNA, indicating that the repeats are a liability to the genomic integrity of a cell. However, little is known about how cells deal with DNA double-stranded breaks in rDNA. Using selective endonucleases, we show that human cells are highly sensitive to breaks in 45S but not the 5S rDNA repeats. We find that homologous recombination inhibits repair of breaks in 45S rDNA, and this results in repeat loss. We identify the structural maintenance of chromosomes protein 5 (SMC5) as contributing to recombination-mediated repair of rDNA breaks. Together, our data demonstrate that SMC5-mediated recombination can lead to error-prone repair of 45S rDNA repeats, resulting in their loss and thereby reducing cellular viability.

Original languageEnglish
Pages (from-to)2519-2527
Number of pages9
JournalCell reports
Volume14
Issue number11
Publication statusPublished - 22-Mar-2016

    Keywords

  • DOUBLE-STRAND BREAKS, DNA-DAMAGE RESPONSE, RNA GENE REPEATS, HOMOLOGOUS RECOMBINATION, SMC5-SMC6 COMPLEX, REPAIR, NUCLEOLUS, CHROMATIN, ATM, END

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