title: RTEL1 contributes to DNA replication and repair and telomere maintenance.
abstract: Telomere maintenance and DNA repair are important processes that protect the genome against instability. mRtel1, an essential helicase, is a dominant factor setting telomere length in mice. In addition, mRtel1 is involved in DNA double-strand break repair. The role of mRtel1 in telomere maintenance and genome stability is poorly understood. Therefore we used mRtel1-deficient mouse embryonic stem cells to examine the function of mRtel1 in replication, DNA repair, recombination, and telomere maintenance. mRtel1-deficient mouse embryonic stem cells showed sensitivity to a range of DNA-damaging agents, highlighting its role in replication and genome maintenance. Deletion of mRtel1 increased the frequency of sister chromatid exchange events and suppressed gene replacement, demonstrating the involvement of the protein in homologous recombination. mRtel1 localized transiently at telomeres and is needed for efficient telomere replication. Of interest, in the absence of mRtel1, telomeres in embryonic stem cells appeared relatively stable in length, suggesting that mRtel1 is required to allow extension by telomerase. We propose that mRtel1 is a key protein for DNA replication, recombination, and repair and efficient elongation of telomeres by telomerase.
authors.affiliation: Terry Fox Laboratory, BC Cancer Agency, Vancouver, BC, Canada.
authors.forename: Evert-Jan
authors.initials: EJ
authors.lastname: Uringa
authors.forename: Kathleen
authors.initials: K
authors.lastname: Lisaingo
authors.forename: Hilda A
authors.initials: HA
authors.lastname: Pickett
authors.forename: Julie
authors.initials: J
authors.lastname: Brind'Amour
authors.forename: Jan-Hendrik
authors.initials: JH
authors.lastname: Rohde
authors.forename: Alex
authors.initials: A
authors.lastname: Zelensky
authors.forename: Jeroen
authors.initials: J
authors.lastname: Essers
authors.forename: Peter M
authors.initials: PM
authors.lastname: Lansdorp
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000235:genetics; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D055879:Gene Knock-In Techniques; D042822:Genomic Instability; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012854:Sister Chromatid Exchange; D019098:Telomerase / Q000378:metabolism; D016615:Telomere / Q000502:physiology*; D059505:Telomere Homeostasis
chemical_list: D004247:DNA; D019098:Telomerase; C527736:regulator of telomere length protein, mouse; D004265:DNA Helicases