T rypanosoma brucei Orc 1 is essential for nuclear DNA replication and affects both VSG silencing and VSG switching
Summary Binding of the O rigin R ecognition C omplex ( 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. T rypanosoma brucei, a protozoan p...
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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 |
01.01.2013
|
Online Access | Get full text |
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Summary: | Summary
Binding of the
O
rigin
R
ecognition
C
omplex (
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.
T
rypanosoma brucei,
a protozoan parasite that causes human
A
frican trypanosomiasis, uses antigenic variation as a major virulence mechanism to evade the host's immune attack by expressing its major surface antigen, the
V
ariant
S
urface
G
lycoprotein (
VSG
), in a monoallelic manner. An
Orc
1/
Cdc
6 homologue 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
TbOrc
1 is essential for nuclear
DNA
replication in mammalian‐infectious bloodstream and tsetse procyclic forms (
BF
and
PF
). Depletion of
TbOrc
1 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.
TbOrc
1 associates with telomere repeats but appears to do so independently of two known
T
. brucei
telomere proteins,
TbRAP
1 and
TbTRF
. We conclude that
TbOrc
1 has conserved functions in
DNA
replication and is also required to control telomere‐linked
VSG
expression and
VSG
switching. |
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ISSN: | 0950-382X 1365-2958 |
DOI: | 10.1111/mmi.12093 |