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 730-734 7 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 730-734 7 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. Fig 1a How can you measure transcription?

10. Fig 1a DNA damage inhibits rRNA transciption 0 Gy10 Gy

11. Fig 1a More irradiation leads to less transcription

12. Fig 1b Transcription arrest is transitory

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

14. Fig 2a 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?

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

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

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

18. DNA damage arrests rRNA transcription via MDC1 and ATM