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Nucleotide excision repair in T rypanosoma brucei : specialization of transcription‐coupled repair due to multigenic transcription
Summary Nucleotide excision repair ( NER ) is a highly conserved genome repair pathway acting on helix distorting DNA lesions. NER is divided into two subpathways: global genome NER ( GG‐NER ), which is responsible for repair throughout genomes, and transcription‐coupled NER ( TC‐NER ), which acts o...
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Published in: | Molecular microbiology 2014-05, Vol.92 (4), p.756-776 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Summary
Nucleotide excision repair (
NER
) is a highly conserved genome repair pathway acting on helix distorting
DNA
lesions.
NER
is divided into two subpathways: global genome
NER
(
GG‐NER
), which is responsible for repair throughout genomes, and transcription‐coupled
NER
(
TC‐NER
), which acts on lesions that impede transcription. The extent of the
T
rypanosoma brucei
genome that is transcribed is highly unusual, since most genes are organized in multigene transcription units, each transcribed from a single promoter. Given this transcription organization, we have addressed the importance of
NER
to
T
. brucei
genome maintenance by performing
RNAi
against all predicted contributing factors. Our results indicate that
TC‐NER
is the main pathway of
NER
repair, but only
CSB
,
XPBz
and
XPG
contribute. Moreover, we show that
UV
lesions are inefficiently repaired in
T
. brucei
, perhaps due to preferential use of
RNA
polymerase translesion synthesis.
RNAi
of
XPC
and
DDB
was found to be lethal, and we show that these factors act in inter‐strand cross‐link repair.
XPD
and
XPB
appear only to act in transcription, not repair. This work indicates that the predominance of multigenic transcription in
T
. brucei
has resulted in pronounced adaptation of
NER
relative to the host and may be an attractive drug target. |
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ISSN: | 0950-382X 1365-2958 |
DOI: | 10.1111/mmi.12589 |