Cell Physiology of Disease Lecture #4 DNA and Viral Genome Replication Initiation of DNA Replication (S Phase) Replication Machinery (Nuclear and Viral) Errors and Proofreading Integration

Steps in DNA Replication Activation of Replication 2. Binding of Initiator Complex to Origin Site (only 2 old strands) 3. Helicase Binding and Opening of Loop 4. Binding of 2 Polymerase Complexes for Leading Strands 5. Primase binding and synthesis of RNA primer 6. Okazaki Fragment Polymerase Binding 7. Degradation of RNA primer 8. Completion of Fragment Synthesis and Annealing

1. Activation of Replication Checkpoints for S Phase Cyclin levels climb during G1 and trigger a cascade to start S 2. Cyclin dependent kinases (Cdk2, 4 & 6) receive signal from level of cyclins (cyclin D & E) and other cues. 3. Fusion studies show that fusion of S cell with G1 cell will start S; however, G2 and S fusion will not enter S.

Replication Timing Does the whole genome get replicated at the same time?

HIV Reverse Transcriptase Structure

HIV Reverse Transcription Many steps are involved in the production of a double stranded DNA from the viral RNA

Proofreading of Replication Polymerase is relatively inaccurate 1 error in 10,000 Proofreading mechanisms enable 1 in 1,000,000.000 3. Cytoplasmic polymerase does not allow proofreading

Integration and Transposition

Mechanism of Integration of HIV

Future Readings, Visiting Lecturer and Original Literature Reading for Next Time on Transcription Chapter 7 of MBOC 4 or equivalent Dr. Jeremy Luban, Director of AIDs Center at Columbia Med, will speak on Mon. Feb 9, on AIDS virus Original Literature: You can get more information on the cell biology by looking at the PubMed web site (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed) and then find the paper with the authors last names (separated by commas). Instructions on links are in the notes.