Nuclear import of Cdc13 limits chromosomal capping

被引:8
|
作者
Mersaoui, Sofiane Y. [1 ,2 ,3 ]
Bonnell, Erin [1 ]
Wellinger, Raymund J. [1 ]
机构
[1] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Microbiol & Infectiol, 3201 Rue Jean Mignault, Sherbrooke, PQ J1E 4K8, Canada
[2] McGill Univ, Lady Davis Inst Med Res, Dept Oncol, Montreal, PQ, Canada
[3] McGill Univ, Lady Davis Inst Med Res, Dept Med, Montreal, PQ, Canada
基金
加拿大健康研究院;
关键词
SINGLE-STRANDED-DNA; MAINTENANCE COMPONENT 1; CAUSE COATS PLUS; TELOMERE MAINTENANCE; SACCHAROMYCES-CEREVISIAE; BINDING PROTEIN; CATALYTIC SUBUNIT; LENGTH REGULATION; YEAST TELOMERASE; POLYMERASE ALPHA;
D O I
10.1093/nar/gky085
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cdc13 is an essential protein involved in telomere maintenance and chromosome capping. Individual domain analyses on Cdc13 suggest the presence of four distinct OB-fold domains and one recruitment domain. However, it remained unclear how these sub-domains function in the context of the whole protein in vivo. Here, we use individual single domain deletions to address their roles in telomere capping. We find that the OB2 domain contains a nuclear localization signal that is essential for nuclear import of Cdc13 and therefore is required for chromosome capping. The karyopherin Msn5 is important for nuclear localization, and retention of Cdc13 in the nucleus also requires its binding to telomeres. Moreover, Cdc13 homodimerization occurs even if the protein is not bound to DNA and is in the cytoplasm. Hence, Cdc13 abundance in the nucleus and, in consequence, its capping function is strongly affected by nucleo-cytoplasmic transport as well as nuclear retention by DNA binding.
引用
收藏
页码:2975 / 2989
页数:15
相关论文
共 50 条
  • [21] Novel alleles of cdc13 and cdc2 isolated as suppressors of mitotic catastrophe in Schizosaccharomyces pombe
    Berry, LD
    Gould, KL
    MOLECULAR AND GENERAL GENETICS, 1996, 251 (06): : 635 - 646
  • [22] Recognition of single-stranded DNA at telomeres by the essential protein Cdc13
    Wuttke, DS
    Anderson, EM
    Halsey, WA
    Lundblad, V
    Mitton-Fry, RM
    Theobald, DL
    PROTEIN SCIENCE, 2004, 13 : 120 - 120
  • [23] Modulation of yeast telomerase activity by Cdc13 and Est1 in vitro
    Chen, Yu-Fan
    Lu, Chia-Ying
    Lin, Yi-Chien
    Yu, Tai-Yuan
    Chang, Chun-Ping
    Li, Jing-Ru
    Li, Hung-Wen
    Lin, Jing-Jer
    SCIENTIFIC REPORTS, 2016, 6
  • [24] Modulation of yeast telomerase activity by Cdc13 and Est1 in vitro
    Yu-Fan Chen
    Chia-Ying Lu
    Yi-Chien Lin
    Tai-Yuan Yu
    Chun-Ping Chang
    Jing-Ru Li
    Hung-Wen Li
    Jing-Jer Lin
    Scientific Reports, 6
  • [25] Cdc13 exhibits dynamic DNA strand exchange in the presence of telomeric DNA
    Nickens, David G.
    Feng, Zhitong
    Shen, Jiangchuan
    Gray, Spencer J.
    Simmons, Robert H.
    Niu, Hengyao
    Bochman, Matthew L.
    NUCLEIC ACIDS RESEARCH, 2024, 52 (11) : 6317 - 6332
  • [26] Mrc1, a non-essential DNA replication protein, is required for telomere end protection following loss of capping by Cdc13, Yku or telomerase
    Nathalie Grandin
    Michel Charbonneau
    Molecular Genetics and Genomics, 2007, 277 : 685 - 699
  • [27] The Cdc48 Protein and Its Cofactor Vms1 Are Involved in Cdc13 Protein Degradation
    Baek, Guem Hee
    Cheng, Haili
    Kim, Ikjin
    Rao, Hai
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2012, 287 (32) : 26788 - 26795
  • [28] Activity of Cdc2 and its interaction with the cyclin Cdc13 depend on the molecular chaperone Cdc37 in Schizosaccharomyces pombe
    Turnbull, EL
    Martin, IV
    Fantes, PA
    JOURNAL OF CELL SCIENCE, 2006, 119 (02) : 292 - 302
  • [29] Analyses of Candida Cdc13 Orthologues Revealed a Novel OB Fold Dimer Arrangement, Dimerization-Assisted DNA Binding, and Substantial Structural Differences between Cdc13 and RPA70
    Yu, Eun Young
    Sun, Jia
    Lei, Ming
    Lue, Neal F.
    MOLECULAR AND CELLULAR BIOLOGY, 2012, 32 (01) : 186 - 198
  • [30] Mrc1, a non-essential DNA replication protein, is required for telomere end protection following loss of capping by Cdc13, Yku or telomerase
    Grandin, Nathalie
    Charbonneau, Michel
    MOLECULAR GENETICS AND GENOMICS, 2007, 277 (06) : 685 - 699