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 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 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 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

Fig 1a How can you measure transcription?

Fig 1a DNA damage inhibits rRNA transciption 0 Gy10 Gy

Fig 1a More irradiation leads to less transcription

Fig 1b Transcription arrest is transitory

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

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?

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

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

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

DNA damage arrests rRNA transcription via MDC1 and ATM