•Exam #1 is Th 9/27 from 7:30 to 9pm(bring cheat sheet)

The ATM repair pathway inhibits RNA polymerase I transcription in response to chromosome breaksMichael Kruhlak, Elizabeth E. Crouch, Marika Orlov, Carolina Montano, Stanislaw A. Gorski, Andre Nussenzweig, Tom Misteli, Robert D. Phair & Rafael Casellas

Nature Vol 447 pg 730-7347 June 2007

How does DNA damage affect transcription?

The ATM repair pathway inhibits RNA polymerase I transcription in response to chromosome breaksMichael Kruhlak, Elizabeth E. Crouch, Marika Orlov, Carolina Montano, Stanislaw A. Gorski, Andre Nussenzweig, Tom Misteli, Robert D. Phair & Rafael Casellas

Nature Vol 447 pg 730-7347 June 2007

rRNA is transcribed by RNA polymerase I

comprised of rRNA

rDNA and transcription of rRNA

rDNA is arranged in repeated transcription units

One transcript is then processed into the three major components of ribosomes

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Fig 1a

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

Fig 1b

Transcription arrest is transitory

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Fig 1c

DNA damage by laser. Only damaged nucleoli show decreased transcription.

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Fig2a

Ku has been shown in vitro to inhibit RNA pol I after DNA damage.

Atm kinase is part of signal transduction following DNA breaks.

What cellular components are involved?

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Fig 2b

Atm must be phosphorylated to mediate the decrease in transcription

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Fig 2c

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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DNA damage arrests rRNA transcription via MDC1 and ATM