title: Human RECQL1 participates in telomere maintenance.
abstract: A variety of human tumors employ alternative and recombination-mediated lengthening for telomere maintenance (ALT). Human RecQ helicases, such as BLM and WRN, can efficiently unwind alternate/secondary structures during telomere replication and/or recombination. Here, we report a novel role for RECQL1, the most abundant human RecQ helicase but functionally least studied, in telomere maintenance. RECQL1 associates with telomeres in ALT cells and actively resolves telomeric D-loops and Holliday junction substrates. RECQL1 physically and functionally interacts with telomere repeat-binding factor 2 that in turn regulates its helicase activity on telomeric substrates. The telomeric single-stranded binding protein, protection of telomeres 1 efficiently stimulates RECQL1 on telomeric substrates containing thymine glycol, a replicative blocking lesion. Loss of RECQL1 results in dysfunctional telomeres, telomere loss and telomere shortening, elevation of telomere sister-chromatid exchanges and increased aphidicolin-induced telomere fragility, indicating a role for RECQL1 in telomere maintenance. Further, our results indicate that RECQL1 may participate in the same pathway as WRN, probably in telomere replication.
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA.
authors.forename: Venkateswarlu
authors.initials: V
authors.lastname: Popuri
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hsu
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA.
authors.forename: Prabhat
authors.initials: P
authors.lastname: Khadka
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA.
authors.forename: Kent
authors.initials: K
authors.lastname: Horvath
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA.
authors.forename: Yie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA.
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Croteau
authors.affiliation: Laboratory of Molecular Gerontology, National Institute on Aging, National Institutes of Health, 251 Bayview Blvd, Suite 100, Baltimore, MD 21224, USA.
authors.forename: Vilhelm A
authors.initials: VA
authors.lastname: Bohr
mesh_terms: D000818:Animals; D004261:DNA Replication; D024202:Electrophoretic Mobility Shift Assay; D005090:Exodeoxyribonucleases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D011485:Protein Binding; D021381:Protein Transport; D053484:RecQ Helicases / Q000378:metabolism / Q000502:physiology*; D019098:Telomerase / Q000378:metabolism; D059505:Telomere Homeostasis; D035341:Telomeric Repeat Binding Protein 2 / Q000378:metabolism; D000071657:Werner Syndrome Helicase
chemical_list: C504753:TERF2 protein, human; D035341:Telomeric Repeat Binding Protein 2; D019098:Telomerase; D005090:Exodeoxyribonucleases; D053484:RecQ Helicases; C098785:WRN protein, human; D000071657:Werner Syndrome Helicase