Trypanosoma brucei Orc1 Is Essential for Nuclear DNA Replication and Affects Both VSG Silencing and Switching
Binding of the Origin Recognition Complex (ORC) to replication origins is essential for initiation of DNA replication, but ORC has non-essential functions outside of DNA replication, including in heterochromatic gene silencing and telomere maintenance. Trypanosoma brucei, a protozoan parasite that c...
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Published in | Molecular microbiology Vol. 87; no. 1; pp. 196 - 210 |
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Main Authors | , , , , , , |
Format | Journal Article |
Language | English |
Published |
10.12.2012
|
Online Access | Get full text |
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Summary: | Binding of the Origin Recognition Complex (ORC) to replication origins is essential for initiation of DNA replication, but ORC has non-essential functions outside of DNA replication, including in heterochromatic gene silencing and telomere maintenance.
Trypanosoma brucei,
a protozoan parasite that causes human African trypanosomiasis, uses antigenic variation as a major virulence mechanism to evade the host’s immune attack by expressing its major surface antigen, the Variant Surface Glycoprotein (VSG), in a monoallelic manner. An Orc1/Cdc6 homolog has been identified in
T. brucei,
but its role in DNA replication has not been directly confirmed and its potential involvement in
VSG
repression or switching has not been thoroughly investigated. In this study, we show that TbOrc1 is essential for nuclear DNA replication in mammalian-infectious bloodstream and tsetse procyclic forms (BF and PF). Depletion of TbOrc1 resulted in derepression of telomere-linked silent
VSG
s in both BF and PF, and increased
VSG
switching particularly through the
in-situ
transcriptional switching mechanism. TbOrc1 associates with telomere repeats but appears to do so independently of two known
T. brucei
telomere proteins, TbRAP1 and TbTRF. We conclude that TbOrc1 has conserved functions in DNA replication and is also required to control telomere-linked
VSG
expression and
VSG
switching. |
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Bibliography: | These authors contributed equally |
ISSN: | 0950-382X 1365-2958 |
DOI: | 10.1111/mmi.12093 |