Trypanosoma brucei UMSBP2 is a single-stranded telomeric DNA binding protein essential for chromosome end protection

Olga Klebanov-Akopyan, Amartya Mishra, Galina Glousker, Yehuda Tzfati, Joseph Shlomai*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Universal minicircle sequence binding proteins (UMSBPs) are CCHC-type zinc-finger proteins that bind a single-stranded G-rich sequence, UMS, conserved at the replication origins of the mitochondrial (kinetoplast) DNA of trypanosomatids. Here, we report that Trypanosoma brucei TbUMSBP2, which has been previously proposed to function in the replication and segregation of the mitochondrial DNA, colocalizes with telomeres at the nucleus and is essential for their structure, protection and function. Knockdown of TbUMSBP2 resulted in telomere clustering in one or few foci, phosphorylation of histone H2A at the vicinity of the telomeres, impaired nuclear division, endoreduplication and cell growth arrest. Furthermore, TbUMSBP2 depletion caused rapid reduction in the G-rich telomeric overhang, and an increase in C-rich single-stranded telomeric DNA and in extrachromosomal telomeric circles. These results indicate that TbUMSBP2 is essential for the integrity and function of telomeres. The sequence similarity between the mitochondrial UMS and the telomeric overhang and the finding that UMSBPs bind both sequences suggest a common origin and/or function of these interactions in the replication and maintenance of the genomes in the two organelles. This feature could have converged or preserved during the evolution of the nuclear and mitochondrial genomes from their ancestral (likely circular) genome in early diverged protists.

Original languageAmerican English
Pages (from-to)7757-7771
Number of pages15
JournalNucleic Acids Research
Volume46
Issue number15
DOIs
StatePublished - 6 Sep 2018

Bibliographical note

Funding Information:
United States-Israel Binational Science Foundation [2011156 to J.S., 2013344 to Y.T.]; Israel Science Foundation [1127/10, 1021/14 to J.S., 1729/13 to Y.T.]; Worldwide Cancer Research [15-0338 to Y.T.]. Funding for open access charge: Israel Science Foundation [1021/14 to J.S.]; Worldwide Cancer Research [15-0338 to Y.T.]. Conflict of interest statement. None declared.

Publisher Copyright:
© The Author(s) 2018.

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