title: [Recognition of internal (TTAGGG)n repeats by telomeric protein TRF1 and its role in maintenance of chromosomal stability in Chinese hamster cells].
abstract: Mammalian telomeres contain long tandem (TTAGGG)n repeats, which are protected by a complex of different proteins. Telomeric repeat-binding factors TRF1 and TRF2 play the key role in protection of telomeres through the formation of terminal loops (called T-loop). A T-loop isolates the 3' strand telomeric end and with this mechanism protects telomeres from the influence of enzymes of DNA reparation and telomere fusions and also interferes with the interaction of telomerase with telomeres. Many vertebrate species also contain large blocks of (TTAGGG)n sequences in pericentric and interstitial chromosome bands. The Chinese hamster genome contains a total of 18 arrays of these non-telomeric internal (TTAGGG)n sequences (ITs). Chromosome bands containing these arrays are unstable and should be protected with the help of another mechanism, rather than that using telomeres. In this study we analysed association of Green Fluorescent Protein (GFP)-tagged TRF1 in Chinese hamster V79 cells with ITs. We found that in these cells GFP-TRF1 associates with ITs in the interphase nucleus. We detected a little overlap between IT-associated GFP-TRF1 and random DSB sites visualized after the treatment of V79 cells with ionizing radiation. We found that the treatment of V79 cells with WM significantly increases the frequency of spontaneous chromosome aberrations. These WM effects are possible due to inhibiting phosphorylation of TRF1 by ATM. TRF1 is known to be eliminated from telomeres by overexpression of TANK1, which induces TRF1 poly(ADP-ribosyl)ation. We transfected V79 cells by plasmid encoding TANK1 and found that the frequency of chromosome rearrangements increased in these cells independently of their treatment by IR. Taken together, our results suggest that TRF1 may be involved in the sequence-specific protection of internal non-telomeric (TTAGGG)n repeats.
authors.affiliation: Laboratory of Chromosome Stability, Institute of Cytology RAS, 194064 St. Petersburg, Russia.
authors.forename: R I
authors.initials: RI
authors.lastname: Krutilina
authors.forename: A N
authors.initials: AN
authors.lastname: Smirnova
authors.forename: O S
authors.initials: OS
authors.lastname: Mudrak
authors.forename: M P
authors.initials: MP
authors.lastname: Svetlova
authors.forename: N M
authors.initials: NM
authors.lastname: Pleskach
authors.forename: S L
authors.initials: SL
authors.lastname: Oei
authors.forename: E M
authors.initials: EM
authors.lastname: Bradbury
authors.forename: A O
authors.initials: AO
authors.lastname: Zalensky
authors.forename: N V
authors.initials: NV
authors.lastname: Tomilin
mesh_terms: D000818:Animals; D002460:Cell Line / Q000528:radiation effects; D043171:Chromosomal Instability; D006224:Cricetinae; D003412:Cricetulus; D007399:Interphase; D020080:Tandem Repeat Sequences; D038501:Tankyrases / Q000096:biosynthesis / Q000235:genetics; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D035321:Telomeric Repeat Binding Protein 1 / Q000378:metabolism / Q000502:physiology*; D035341:Telomeric Repeat Binding Protein 2 / Q000502:physiology; D014162:Transfection
chemical_list: D035321:Telomeric Repeat Binding Protein 1; D035341:Telomeric Repeat Binding Protein 2; D038501:Tankyrases