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

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 breaks

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

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

  2. 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 730-7347 June 2007

  3. 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 730-7347 June 2007

  4. rRNA is transcribed by RNA polymerase I

  5. comprised of rRNA

  6. rDNA and transcription of rRNA

  7. rDNA is arranged in repeated transcription units

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

  9. How can you measure transcription? Fig 1a

  10. DNA damage inhibits rRNA transciption 0 Gy 10 Gy Fig 1a

  11. More irradiation leads to less transcription Fig 1a

  12. Transcription arrest is transitory Fig 1b

  13. DNA damage by laser. Only damaged nucleoli show decreased transcription. Fig 1c

  14. What cellular components are involved? Ku has been shown in vitro to inhibit RNA pol I after DNA damage. Atm kinase is part of signal transduction following DNA breaks. Fig2a

  15. Atm must be phosphorylated to mediate the decrease in transcription Fig 2b

  16. Mdc1 facilitates recruitment of the ATM kinase and mutants show no transcription arrest following DNA damage Fig 2c

  17. Brca1, H2ax, Ku80, and 53bp1 are involved in DNA repair. Transcription arrest occurs, but resumption is delayed. Fig 2c

  18. DNA damage arrests rRNA transcription via MDC1 and ATM

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