Download The ATM repair pathway inhibits RNA polymerase I transcription in

•Homework #2 is posted and
due 10/17
•Exams should be returned on
W 10/3
Combinations of
3 nucleotides
code for each 1
amino acid in a
protein.
Exons are a very
small part of DNA
Each step in gene
expression presents an
opportunity to regulate
when and how much of
a gene product will be
produced.
In bacteria, transcription and translation occur
simultaneously. So most regulation of gene
expression happens at transcription.
Why change gene
expression?
•Different cells need
different components
•Responding to the
environment
•Replacement of
damaged/worn-out parts
Two points to keep in
mind:
1. Cellular components
are constantly turnedover.
2. Gene expression takes
time:
Typically more than an
hour from DNA to
protein. Most
rapidly 15 minutes.
Blood clotting must happen within minutes
mRNA levels change
in response to cold
acclimation
Fowler and Thomashow
The Plant Cell, Vol. 14, 1675-1690, 2002
•Gene expression can be
controlled at many
points between DNA and
making the final
proteins.
•Changes in the various
steps of gene expression
control when and how
much of a product are
produced.
The ATM repair pathway inhibits RNA
polymerase I transcription in response to
chromosome breaks
Michael Kruhlak, Elizabeth E. Crouch, Marika Orlov, Carolina
Montano, Stanislaw A. Gorski, Andre Nussenzweig, Tom Misteli,
Robert D. Phair & Rafael Casellas
Nature Vol 447 pg 730-734
7 June 2007
How does DNA damage affect transcription?
The ATM repair pathway inhibits RNA
polymerase I transcription in response to
chromosome breaks
Michael Kruhlak, Elizabeth E. Crouch, Marika Orlov, Carolina
Montano, Stanislaw A. Gorski, Andre Nussenzweig, Tom Misteli,
Robert D. Phair & Rafael Casellas
Nature Vol 447 pg 730-734
7 June 2007
rRNA is transcribed by RNA polymerase I
Ribosomes
comprised of
rRNA
How can the cell make enough rRNA and
ensure that equal amounts of the different
rRNAs get produced?
Ribosomes
rDNA and
transcription
of rRNA
rDNA is arranged in
repeated transcription
units
One
transcript
is then
processed
into the
three major
components
of
ribosomes
How can you measure transcription?
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Fig 1a
DNA damage inhibits rRNA transciption
0 Gy
10 Gy
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Fig 1a
More irradiation leads to less transcription
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Fig 1a
Transcription arrest is transitory
Fig 1b
DNA damage by laser. Only damaged
nucleoli show decreased transcription.
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Fig 1c
What cellular components are involved?
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Ku has been shown in
vitro to inhibit RNA pol
I after DNA damage.
Atm kinase is part of
signal transduction
Fig
following DNA breaks. 2a
Atm must be phosphorylated to mediate the
decrease in transcription
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Fig 2b
Mdc1 facilitates recruitment of the ATM
kinase and mutants show no transcription
arrest following DNA damage
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Fig 2c
Brca1, H2ax, Ku80, and 53bp1 are involved in
DNA repair. Transcription arrest occurs, but
resumption is delayed.
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Fig 2c
DNA damage arrests rRNA transcription via
MDC1 and ATM
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Each step in gene
expression presents an
opportunity to regulate
when and how much of
a gene product will be
produced.
•Homework #2 is posted and
due 10/17
•Exams should be returned on
W 10/3