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Homework #2 is posted and due 10/17

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1 Homework #2 is posted and due 10/17
Exams should be returned on W 10/3

2 Combinations of 3 nucleotides code for each 1 amino acid in a protein.

3 Exons are a very small part of DNA

4 Each step in gene expression presents an opportunity to regulate when and how much of a gene product will be produced.

5 In bacteria, transcription and translation occur simultaneously
In bacteria, transcription and translation occur simultaneously. So most regulation of gene expression happens at transcription.

6 Why change gene expression?
Different cells need different components Responding to the environment Replacement of damaged/worn-out parts

7 Two points to keep in mind:
Cellular components are constantly turned-over. Gene expression takes time: Typically more than an hour from DNA to protein. Most rapidly 15 minutes.

8 Blood clotting must happen within minutes

9 mRNA levels change in response to cold acclimation
Fowler and Thomashow The Plant Cell, Vol. 14, , 2002

10 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.

11 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

12 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

13 rRNA is transcribed by RNA polymerase I

14 Ribosomes comprised of rRNA

15 How can the cell make enough rRNA and ensure that equal amounts of the different rRNAs get produced?
Ribosomes

16 rDNA and transcription of rRNA

17 rDNA is arranged in repeated transcription units

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

19 How can you measure transcription?
Fig 1a

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

21 More irradiation leads to less transcription
Fig 1a

22 Transcription arrest is transitory
Fig 1b

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

24 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. Fig 2a

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

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

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

28 DNA damage arrests rRNA transcription via MDC1 and ATM

29 Each step in gene expression presents an opportunity to regulate when and how much of a gene product will be produced.

30 Homework #2 is posted and due 10/17
Exams should be returned on W 10/3


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