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RPA prevents G-rich structure formation at lagging-strand telomeres to allow maintenance of chromosome ends.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Audry, Julien Maestroni, Laetitia Delagoutte, Emmanuelle Gauthier, Tiphaine Nakamura, Toru M. Gachet, Yannick Saintomé, Carole Géli, Vincent Coulon, Stéphane |
| Copyright Year | 2015 |
| Abstract | Replication protein A (RPA) is a highly conserved heterotrimeric single-stranded DNA-binding protein involved in DNA replication, recombination, and repair. In fission yeast, the Rpa1-D223Y mutation provokes telomere shortening. Here, we show that this mutation impairs lagging-strand telomere replication and leads to the accumulation of secondary structures and recruitment of the homologous recombination factor Rad52. The presence of these secondary DNA structures correlates with reduced association of shelterin subunits Pot1 and Ccq1 at telomeres. Strikingly, heterologous expression of the budding yeast Pif1 known to efficiently unwind G-quadruplex rescues all the telomeric defects of the D223Y cells. Furthermore, in vitro data show that the identical D to Y mutation in human RPA specifically affects its ability to bind G-quadruplex. We propose that RPA prevents the formation of G-quadruplex structures at lagging-strand telomeres to promote shelterin association and facilitate telomerase action at telomeres. |
| Starting Page | 649 |
| Ending Page | 659 |
| Page Count | 11 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://emboj.embopress.org/content/embojnl/34/14/1942.full.pdf |
| Alternate Webpage(s) | http://embojnl.embopress.org/content/embojnl/34/14/1942.full.pdf |
| Alternate Webpage(s) | http://embojnl.embopress.org/content/embojnl/34/14/1942.reviewer-comments.pdf |
| PubMed reference number | 26041456v1 |
| Alternate Webpage(s) | https://doi.org/10.15252/embj.201490773 |
| DOI | 10.15252/embj.201490773 |
| Journal | The EMBO journal |
| Volume Number | 34 |
| Issue Number | 14 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | DNA Breaks, Single-Stranded DNA Replication G-Quadruplexes Homologous Recombination Mutation POT1 gene Saccharomycetales Schizosaccharomyces pombe Shelterin Telomerase Telomere Shortening |
| Content Type | Text |
| Resource Type | Article |
