1. Yadi Zhou 2013.12.05

2. RecA protein 38 kiloDalton Essential for the repair and maintenance of DNA A RecA structural and functional homolog has been found in every species Homologous protein in Homo sapiens is RAD51 Important enzyme in homologous recombination Induce SOS response

3. Structure

4. RecA filament RecA-dsDNA

5. Homologous recombination

7. SOS response

8. E. coli strains deficient in RecA are useful Potential drug target

9. References http://www.callutheran.edu/BioDev/omm/reca/rec amast.htm http://en.wikipedia.org/wiki/RecA Nature Reviews Molecular Cell Biology 8, 127-138 (February 2007) http://www.callutheran.edu/BioDev/omm/reca/rec amast.htm Nature 453, 463-466(22 May 2008)

11. Mechanisms of RecA DNA Repair Vivian Lesende December 5, 2013 BIOS 7200

12. Can arrest replication --- deletions/genomic rearrangements, point mutations, lethality Many types of lesions can inhibit normal progression of replication forks -UV radiation – cis, syn-cyclobutane pyrimidine dimer (CPD) & pyrimidine-6-4-pyrimidone photoproduct (6-4 PP) DNA Damage

13. RecA functions to recover replication forks in several different ways -acts as transactivator for upregulating over 40 genes (SOS response) -protects single stranded DNA from degradation while replication is arrested -promotes recombination repair RecA Functions

14. LexA -- repressor binds to a 20 bp consensus sequence in operator region in DNA-damage inducible genes RecA bound to damaged single stranded DNA causes autocatalytic cleavage Increases transcription of genes involved in SOS Response SOS Response

15. Genes that function to remove lesions and restore replication uvrA & uvrB -- recognize UV-induced lesions ydjQ (cho) -- incision step for excision repair polB, dinB, umuC & umuD – DNA polymerases Pol II, PolI V, Pol V Genes Involved in SOS Response

16. SOS Response Courcelle & Hanawalt. Annu. Rev. Genet. 2003. 37:611-46

17. RecA maintains structure of replication forks until replication resumes Allows for nucleotide excision repair to occur recA mutants have high sensitivity to UV-light – “rec-less” degradation Prevention of Degradation of Single- Stranded DNA of Replication Forks

18. Courcelle & Hanawalt. Annu. Rev. Genet. 2003. 37:611-46

19. “postreplication repair” or “daughter-strand gap repair” RecA promotes recombination as an alternative to excision repair – does not remove lesions from DNA Typically only occurs if previous mechanisms have failed Recombination Recovery

20. Courcelle & Hanawalt. Annu. Rev. Genet. 2003. 37:611-46

21. J. Courcelle & P. C. Hanawalt. RecA-Dependent Recovery of Arrested DNA Replication Forks. Annu. Rev. Genet. 2003. 37:611-46 References