TY - JOUR
T1 - Rejuvenation of ribosomal RNA gene repeats at the nuclear pore
AU - Horigome, Chihiro
AU - Kobayashi, Takehiko
N1 - Funding Information:
We regret the omission of many important references due to space constraints. This work was supported by JSPS KAKENHI Grant numbers JP16K20987, JP18K06056 to CH and JP17H01443 to TK ( https://www.jsps.go.jp/english/index.html ) and the Takeda Science Foundation.
Publisher Copyright:
© 2019, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2020/2/1
Y1 - 2020/2/1
N2 - The ribosomal RNA genes (rDNA) exist as tandem repeats in eukaryotes and are, therefore, highly unstable. Each rDNA unit includes a replication fork barrier site to avoid collisions between DNA replication forks and transcriptional machinery. However, because of this barrier, DNA double-strand breaks are induced at a relatively high frequency. If damage is repaired by the homologous recombination in rDNAs, it may result in frequent copy number changes and the production of extrachromosomal ribosomal DNA circles, both of which are closely linked to the regulation of lifespan. Here, we review recent progress in elucidating a multi-layered repair process of rDNA that occurs in the nucleolus, nucleoplasm and nuclear pores. Binding to nuclear pores appears to be the final strategy for repairing any remaining damage to the rDNA. Here, we propose the possible contribution of nuclear pores to the asymmetric distribution of damaged rDNA between mother and daughter cells as well as its possible impact on aging/rejuvenation.
AB - The ribosomal RNA genes (rDNA) exist as tandem repeats in eukaryotes and are, therefore, highly unstable. Each rDNA unit includes a replication fork barrier site to avoid collisions between DNA replication forks and transcriptional machinery. However, because of this barrier, DNA double-strand breaks are induced at a relatively high frequency. If damage is repaired by the homologous recombination in rDNAs, it may result in frequent copy number changes and the production of extrachromosomal ribosomal DNA circles, both of which are closely linked to the regulation of lifespan. Here, we review recent progress in elucidating a multi-layered repair process of rDNA that occurs in the nucleolus, nucleoplasm and nuclear pores. Binding to nuclear pores appears to be the final strategy for repairing any remaining damage to the rDNA. Here, we propose the possible contribution of nuclear pores to the asymmetric distribution of damaged rDNA between mother and daughter cells as well as its possible impact on aging/rejuvenation.
KW - Aging
KW - Asymmetric cell division
KW - DNA damage checkpoint
KW - DNA double-strand break
KW - Nuclear pore
KW - Rejuvenation
KW - Ribosomal RNA gene (rDNA)
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U2 - 10.1007/s00294-019-01024-3
DO - 10.1007/s00294-019-01024-3
M3 - Review article
C2 - 31392389
AN - SCOPUS:85070303544
VL - 66
SP - 7
EP - 13
JO - Current Genetics
JF - Current Genetics
SN - 0172-8083
IS - 1
ER -