title: Replication protein A prevents accumulation of single-stranded telomeric DNA in cells that use alternative lengthening of telomeres.
abstract: The activation of a telomere maintenance mechanism is required for cancer development in humans. While most tumors achieve this by expressing the enzyme telomerase, a fraction (5-15%) employs a recombination-based mechanism termed alternative lengthening of telomeres (ALT). Here we show that loss of the single-stranded DNA-binding protein replication protein A (RPA) in human ALT cells, but not in telomerase-positive cells, causes increased exposure of single-stranded G-rich telomeric DNA, cell cycle arrest in G2/M phase, accumulation of single-stranded telomeric DNA within ALT-associated PML bodies (APBs), and formation of telomeric aggregates at the ends of metaphase chromosomes. This study demonstrates differences between ALT cells and telomerase-positive cells in the requirement for RPA in telomere processing and implicates the ALT mechanism in tumor cells as a possible therapeutic target.
authors.affiliation: Section of Oncology, Department of Medicine, Haukeland University Hospital.
authors.forename: Amra
authors.initials: A
authors.lastname: Grudic
authors.forename: Asne
authors.initials: A
authors.lastname: Jul-Larsen
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Haring
authors.forename: Marc S
authors.initials: MS
authors.lastname: Wold
authors.forename: Per Eystein
authors.initials: PE
authors.lastname: Lønning
authors.forename: Rolf
authors.initials: R
authors.lastname: Bjerkvig
authors.forename: Stig Ove
authors.initials: SO
authors.lastname: Bøe
mesh_terms: D002453:Cell Cycle; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004277:DNA, Single-Stranded / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000235:genetics*; D034622:RNA Interference; D051716:Replication Protein A / Q000037:antagonists & inhibitors / Q000502:physiology*; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*
chemical_list: D004277:DNA, Single-Stranded; D051716:Replication Protein A