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RPA prevents G‐rich structure formation at lagging‐strand telomeres to allow maintenance of chromosome ends
Author(s) -
Audry Julien,
Maestroni Laetitia,
Delagoutte Emmanuelle,
Gauthier Tiphaine,
Nakamura Toru M,
Gachet Yannick,
Saintomé Carole,
Géli Vincent,
Coulon Stéphane
Publication year - 2015
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201490773
Subject(s) - telomere , biology , replication protein a , telomere binding protein , rad52 , shelterin , homologous recombination , telomerase , dna replication , microbiology and biotechnology , dna repair , dna , mutation , genetics , rad51 , dna binding protein , transcription factor , gene
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.