Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae. / Prada-Luengo, Iñigo; Møller, Henrik D.; Henriksen, Rasmus A.; Gao, Qian; Larsen, Camilla Eggert; Alizadeh, Sefa; Maretty, Lasse; Houseley, Jonathan; Regenberg, Birgitte.

In: Nucleic Acids Research, Vol. 48, No. 14, 2020, p. 7883-7898.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Prada-Luengo, I, Møller, HD, Henriksen, RA, Gao, Q, Larsen, CE, Alizadeh, S, Maretty, L, Houseley, J & Regenberg, B 2020, 'Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae', Nucleic Acids Research, vol. 48, no. 14, pp. 7883-7898. https://doi.org/10.1093/nar/gkaa545

APA

Prada-Luengo, I., Møller, H. D., Henriksen, R. A., Gao, Q., Larsen, C. E., Alizadeh, S., Maretty, L., Houseley, J., & Regenberg, B. (2020). Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae. Nucleic Acids Research, 48(14), 7883-7898. https://doi.org/10.1093/nar/gkaa545

Vancouver

Prada-Luengo I, Møller HD, Henriksen RA, Gao Q, Larsen CE, Alizadeh S et al. Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae. Nucleic Acids Research. 2020;48(14):7883-7898. https://doi.org/10.1093/nar/gkaa545

Author

Prada-Luengo, Iñigo ; Møller, Henrik D. ; Henriksen, Rasmus A. ; Gao, Qian ; Larsen, Camilla Eggert ; Alizadeh, Sefa ; Maretty, Lasse ; Houseley, Jonathan ; Regenberg, Birgitte. / Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae. In: Nucleic Acids Research. 2020 ; Vol. 48, No. 14. pp. 7883-7898.

Bibtex

@article{1a402ef597a14b9f8ab0d69b12adf73c,
title = "Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae",
abstract = "Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular DNA in Saccharomyces cerevisiae populations sampled when young and after extensive aging. Young cells possessed highly diverse circular DNA populations but 94% of the circular DNA were lost after ∼15 divisions, whereas rDNA circles underwent massive accumulation to >95% of circular DNA. Circles present in both young and old cells were characterized by replication origins including circles from unique regions of the genome and repetitive regions: rDNA and telomeric Y' regions. We further observed that circles can have flexible inheritance patterns: [HXT6/7circle] normally segregates to mother cells but in low glucose is present in up to 50% of cells, the majority of which must have inherited this circle from their mother. Interestingly, [HXT6/7circle] cells are eventually replaced by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNAs are intermediates in chromosomal amplifications. In conclusion, the heterogeneity of circular DNA offers flexibility in adaptation, but this heterogeneity is remarkably diminished with age.",
author = "I{\~n}igo Prada-Luengo and M{\o}ller, {Henrik D.} and Henriksen, {Rasmus A.} and Qian Gao and Larsen, {Camilla Eggert} and Sefa Alizadeh and Lasse Maretty and Jonathan Houseley and Birgitte Regenberg",
year = "2020",
doi = "10.1093/nar/gkaa545",
language = "English",
volume = "48",
pages = "7883--7898",
journal = "Nucleic Acids Research",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "14",

}

RIS

TY - JOUR

T1 - Replicative aging is associated with loss of genetic heterogeneity from extrachromosomal circular DNA in Saccharomyces cerevisiae

AU - Prada-Luengo, Iñigo

AU - Møller, Henrik D.

AU - Henriksen, Rasmus A.

AU - Gao, Qian

AU - Larsen, Camilla Eggert

AU - Alizadeh, Sefa

AU - Maretty, Lasse

AU - Houseley, Jonathan

AU - Regenberg, Birgitte

PY - 2020

Y1 - 2020

N2 - Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular DNA in Saccharomyces cerevisiae populations sampled when young and after extensive aging. Young cells possessed highly diverse circular DNA populations but 94% of the circular DNA were lost after ∼15 divisions, whereas rDNA circles underwent massive accumulation to >95% of circular DNA. Circles present in both young and old cells were characterized by replication origins including circles from unique regions of the genome and repetitive regions: rDNA and telomeric Y' regions. We further observed that circles can have flexible inheritance patterns: [HXT6/7circle] normally segregates to mother cells but in low glucose is present in up to 50% of cells, the majority of which must have inherited this circle from their mother. Interestingly, [HXT6/7circle] cells are eventually replaced by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNAs are intermediates in chromosomal amplifications. In conclusion, the heterogeneity of circular DNA offers flexibility in adaptation, but this heterogeneity is remarkably diminished with age.

AB - Circular DNA can arise from all parts of eukaryotic chromosomes. In yeast, circular ribosomal DNA (rDNA) accumulates dramatically as cells age, however little is known about the accumulation of other chromosome-derived circles or the contribution of such circles to genetic variation in aged cells. We profiled circular DNA in Saccharomyces cerevisiae populations sampled when young and after extensive aging. Young cells possessed highly diverse circular DNA populations but 94% of the circular DNA were lost after ∼15 divisions, whereas rDNA circles underwent massive accumulation to >95% of circular DNA. Circles present in both young and old cells were characterized by replication origins including circles from unique regions of the genome and repetitive regions: rDNA and telomeric Y' regions. We further observed that circles can have flexible inheritance patterns: [HXT6/7circle] normally segregates to mother cells but in low glucose is present in up to 50% of cells, the majority of which must have inherited this circle from their mother. Interestingly, [HXT6/7circle] cells are eventually replaced by cells carrying stable chromosomal HXT6 HXT6/7 HXT7 amplifications, suggesting circular DNAs are intermediates in chromosomal amplifications. In conclusion, the heterogeneity of circular DNA offers flexibility in adaptation, but this heterogeneity is remarkably diminished with age.

U2 - 10.1093/nar/gkaa545

DO - 10.1093/nar/gkaa545

M3 - Journal article

C2 - 32609810

AN - SCOPUS:85089709269

VL - 48

SP - 7883

EP - 7898

JO - Nucleic Acids Research

JF - Nucleic Acids Research

SN - 0305-1048

IS - 14

ER -

ID: 248190043