title: Nucleostemin inhibits TRF1 dimerization and shortens its dynamic association with the telomere.
abstract: TRF1 is a key component of the telomere-capping complex and binds double-strand telomeric DNA as homodimers. So far, it is not clear whether TRF1 dimerization coincides with its telomere binding or is actively controlled before it binds the telomere, and in the latter case, how this event might affect its telomere association. We previously found that TRF1 dimerization and its telomere binding can be increased by GNL3L, which is the vertebrate paralogue of nucleostemin (NS). Here, we show that NS and GNL3L bind TRF1 directly but competitively through two separate domains of TRF1. In contrast to GNL3L, NS prevents TRF1 dimerization through a mechanism not determined by its ability to displace TRF1-bound GNL3L. Furthermore, NS is capable of shortening the dynamic association of TRF1 with the telomere in normal and TRF2(ΔBΔM)-induced telomere-damaged cells without affecting the amount of telomere-bound TRF1 proteins in vivo. Importantly, NS displays a protective function against the formation of telomere-dysfunction-induced foci. This work demonstrates that TRF1 dimerization is actively and oppositely regulated by NS and GNL3L extrachromosomally. Changing the relative amount of TRF1 monomers versus dimers in the nucleoplasm might affect the dynamic association of TRF1 with the telomere and the repair of damaged telomeres.
authors: Institute of Biosciences and Technology, Texas A&M Health Science Center, Houston, Texas 77030, USA.
authors: Lingjun
authors: L
authors: Meng
authors: Joseph K
authors: JK
authors: Hsu
authors: Qubo
authors: Q
authors: Zhu
authors: Tao
authors: T
authors: Lin
authors: Robert Y L
authors: RY
authors: Tsai
mesh_terms: D002460:Cell Line; D019281:Dimerization; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016615:Telomere / Q000235:genetics / Q000378:metabolism*; D035321:Telomeric Repeat Binding Protein 1 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: C469949:GNL3 protein, human; C509155:GNL3L protein, human; D009687:Nuclear Proteins; D035321:Telomeric Repeat Binding Protein 1; D019204:GTP-Binding Proteins