Structure, dynamics, and regulation of TRF1-TIN2-mediated trans- and cis-interactions on telomeric DNA
DC Element | Wert | Sprache |
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dc.contributor.author | Pan, Hai | |
dc.contributor.author | Kaur, Parminder | |
dc.contributor.author | Barnes, Ryan | |
dc.contributor.author | Detwiler, Ariana C. | |
dc.contributor.author | Sanford, Samantha Lynn | |
dc.contributor.author | Liu, Ming | |
dc.contributor.author | Xu, Pengning | |
dc.contributor.author | Mahn, Chelsea | |
dc.contributor.author | Tang, Qingyu | |
dc.contributor.author | Hao, Pengyu | |
dc.contributor.author | Bhattaram, Dhruv | |
dc.contributor.author | You, Changjiang | |
dc.contributor.author | Gu, Xinyun | |
dc.contributor.author | Lu, Warren | |
dc.contributor.author | Piehler, Jacob | |
dc.contributor.author | Xu, Guozhou | |
dc.contributor.author | Weninger, Keith | |
dc.contributor.author | Riehn, Robert | |
dc.contributor.author | Opresko, Patricia L. | |
dc.contributor.author | Wang, Hong | |
dc.date.accessioned | 2021-12-23T16:23:39Z | - |
dc.date.available | 2021-12-23T16:23:39Z | - |
dc.date.issued | 2021 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/14618 | - |
dc.description.abstract | TIN2 is a core component of the shelterin complex linking double-stranded telomeric DNA-binding proteins (TRF1 and TRF2) and single-strand overhang-binding proteins (TPP1-POT1). In vivo, the large majority of TRF1 and TRF2 exist in complexes containing TIN2 but lacking TPP1/POT1; however, the role of TRF1-TIN2 interactions in mediating interactions with telomeric DNA is unclear. Here, we investigated DNA molecular structures promoted by TRF1-TIN2 interaction using atomic force microscopy (AFM), total internal reflection fluo-rescence microscopy (TIRFM), and the DNA tightrope assay. We demonstrate that the short (TIN2S) and long (TIN2L) isoforms of TIN2 facilitate TRF1-mediated DNA compaction (cis-in-teractions) and DNA-DNA bridging (trans-interactions) in a telomeric sequence-and length-dependent manner. On the short telomeric DNA substrate (six TTAGGG repeats), the ma-jority of TRF1-mediated telomeric DNA-DNA bridging events are transient with a lifetime of similar to 1.95 s. On longer DNA substrates (270 TTAGGG repeats), TIN2 forms multiprotein complexes with TRF1 and stabilizes TRF1-mediated DNA-DNA bridging events that last on the order of minutes. Preincubation of TRF1 with its regulator protein Tankyrase 1 and the cofactor NAD+ significantly reduced TRF1-TIN2 mediated DNA-DNA bridging, whereas TIN2 protected the disassembly of TRF1-TIN2 mediated DNA-DNA bridging upon Tankyrase 1 addition. Furthermore, we showed that TPP1 inhibits TRF1-TIN2L-mediated DNA-DNA bridging. Our study, together with previous findings, supports a molecular model in which protein assemblies at telomeres are heterogeneous with distinct subcomplexes and full shelterin complexes playing distinct roles in telomere protection and elongation. | |
dc.description.sponsorship | National Institutes of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [R01GM107559, R01GM123246, P30 ES025128, R01CA207342, R01GM132263]; This work was supported by the National Institutes of Health (R01GM107559 to H. W., R. R., R01GM123246 to H. W., R. R., and P. L. O, P30 ES025128 Pilot Project Grant to H. W. and P. K. through the Center for Human Health and the Environment at NCSU, R01CA207342 to P.L.O., and R01GM132263 to K.W.) . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. | |
dc.language.iso | en | |
dc.publisher | ELSEVIER | |
dc.relation.ispartof | JOURNAL OF BIOLOGICAL CHEMISTRY | |
dc.subject | BINDING PROTEIN | |
dc.subject | Biochemistry & Molecular Biology | |
dc.subject | COMPLEX | |
dc.subject | END | |
dc.subject | LENGTH REGULATOR | |
dc.subject | MECHANISM | |
dc.subject | PROTECTION | |
dc.subject | PROTEIN TIN2 | |
dc.subject | SHELTERIN | |
dc.subject | SINGLE-MOLECULE | |
dc.subject | TRF1 | |
dc.title | Structure, dynamics, and regulation of TRF1-TIN2-mediated trans- and cis-interactions on telomeric DNA | |
dc.type | journal article | |
dc.identifier.doi | 10.1016/j.jbc.2021.101080 | |
dc.identifier.isi | ISI:000706409200005 | |
dc.description.volume | 297 | |
dc.description.issue | 3 | |
dc.contributor.orcid | 0000-0003-0165-3559 | |
dc.contributor.orcid | 0000-0002-6517-3557 | |
dc.contributor.orcid | 0000-0002-4408-3560 | |
dc.contributor.orcid | 0000-0002-9311-5899 | |
dc.contributor.orcid | 0000-0002-5554-6540 | |
dc.contributor.researcherid | F-3164-2014 | |
dc.contributor.researcherid | A-7195-2011 | |
dc.contributor.researcherid | W-4530-2018 | |
dc.identifier.eissn | 1083351X | |
dc.publisher.place | RADARWEG 29, 1043 NX AMSTERDAM, NETHERLANDS | |
dcterms.isPartOf.abbreviation | J. Biol. Chem. | |
dcterms.oaStatus | gold, Green Published | |
crisitem.author.dept | Sonderforschungsbereich 944: Physiologie und Dynamik zellulärer Mikrokompartimente | - |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | organisation19 | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.orcid | 0000-0002-7839-6397 | - |
crisitem.author.orcid | 0000-0002-2143-2270 | - |
crisitem.author.parentorg | FB 05 - Biologie/Chemie | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.grandparentorg | Universität Osnabrück | - |
crisitem.author.netid | YoCh745 | - |
crisitem.author.netid | PiJa938 | - |
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