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

APA

Warmerdam, D. O., van den Berg, J., & Medema, R. H. (2016). Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats. Cell reports, 14(11), 2519-2527. https://doi.org/10.1016/j.celrep.2016.02.048

Author

Warmerdam, Daniel O. ; van den Berg, Jeroen ; Medema, Rene H. / Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats. In: Cell reports. 2016 ; Vol. 14, No. 11. pp. 2519-2527.

Harvard

Warmerdam, DO, van den Berg, J & Medema, RH 2016, 'Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats' Cell reports, vol. 14, no. 11, pp. 2519-2527. https://doi.org/10.1016/j.celrep.2016.02.048

Standard

Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats. / Warmerdam, Daniel O.; van den Berg, Jeroen; Medema, Rene H.

In: Cell reports, Vol. 14, No. 11, 22.03.2016, p. 2519-2527.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Warmerdam DO, van den Berg J, Medema RH. Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats. Cell reports. 2016 Mar 22;14(11):2519-2527. https://doi.org/10.1016/j.celrep.2016.02.048


BibTeX

@article{18f748def4754596af356102ed9a7ced,
title = "Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats",
abstract = "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.",
keywords = "DOUBLE-STRAND BREAKS, DNA-DAMAGE RESPONSE, RNA GENE REPEATS, HOMOLOGOUS RECOMBINATION, SMC5-SMC6 COMPLEX, REPAIR, NUCLEOLUS, CHROMATIN, ATM, END",
author = "Warmerdam, {Daniel O.} and {van den Berg}, Jeroen and Medema, {Rene H.}",
year = "2016",
month = "3",
day = "22",
doi = "10.1016/j.celrep.2016.02.048",
language = "English",
volume = "14",
pages = "2519--2527",
journal = "Cell reports",
issn = "2211-1247",
publisher = "CELL PRESS",
number = "11",

}

RIS

TY - JOUR

T1 - Breaks in the 45S rDNA Lead to Recombination-Mediated Loss of Repeats

AU - Warmerdam, Daniel O.

AU - van den Berg, Jeroen

AU - Medema, Rene H.

PY - 2016/3/22

Y1 - 2016/3/22

N2 - 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.

AB - 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.

KW - DOUBLE-STRAND BREAKS

KW - DNA-DAMAGE RESPONSE

KW - RNA GENE REPEATS

KW - HOMOLOGOUS RECOMBINATION

KW - SMC5-SMC6 COMPLEX

KW - REPAIR

KW - NUCLEOLUS

KW - CHROMATIN

KW - ATM

KW - END

U2 - 10.1016/j.celrep.2016.02.048

DO - 10.1016/j.celrep.2016.02.048

M3 - Article

VL - 14

SP - 2519

EP - 2527

JO - Cell reports

JF - Cell reports

SN - 2211-1247

IS - 11

ER -

ID: 40772493