This information was most recently updated October 30, 2006.
I am not an expert in DNA repair; I simply teach two lectures on the subject to graduate students at Roswell Park Cancer Institute. Except where specifically stated in the lecture notes below, all of the ideas presented in these lecture notes derive from one or the other of the sources in the reading list or from other sources in the literature. Similarly, the illustrations that I have drawn are based on the illustrations in these sources, with minor or major modifications by me.
None of the exam questions on DNA repair will be based on information that is not presented in these lectures. Nevertheless, for your own information and enjoyment, you may wish to do some further reading. Here are some recommendations. I particularly recommend Errol Friedberg's historical overview of the DNA repair field, highlighted in red below:
Recent Reviews (plus a few interesting research articles):
JQ Svejstrup. Mechanisms of transcription-coupled DNA repair. Nature Revs. Mol. Cell Biol. 3:21-29, 2002.
P McGlynn, RG Lloyd. Recombinational repair and restart of damaged replication forks. Nature Revs. Mol. Cell Biol. 3:859-870, 2002.
TJ Begley, LD Samson. AlkB mystery solved: oxidative demethylation of N1-methyladenine and N3-methylcytosine adducts by a direct reversal mechanism. TIBS 28: 2-5, 2003.
EC Friedberg. DNA damage and repair. Nature 421: 436-440, 2003. Recommended.
J Jiricny, G Marra. DNA repair defects in colon cancer. Curr. Opin. Genet. Devel. 13: 61-69, 2003.
JR Mitchell, JHJ Hoeijmakers, LJ Niedernhofer. Divide and conquer: nucleotide excision repair battles cancer and ageing. Curr. Opin. Cell Biol. 15: 232-240, 2003.
SD Cline, PC Hanawalt. Who's on first in the cellular response to DNA damage? Nature Revs. Mol. Cell Biol. 4: 361-372, 2003.
MR Lieber, Y Ma, U Pannicke, K Schwarz. Mechanism and regulation of human non-homologous DNA end-joining. Nature Revs. Mol. Cell Biol. 4: 712-720, 2003.
- Sancar A, Lindsey-Boltz LA, Unsal-Kacmaz K, Linn S. Molecular mechanisms of mammalian DNA repair and the DNA damage checkpoints. Annu Rev Biochem 73: 39-85, 2004.
- Shiloh Y, editor. BRIDGE OVER BROKEN ENDS - The Cellular Response to DNA Breaks in Health and Disease. Special issue of DNA Repair Volume 3, Issues 8-9, Pages 779-1251 (August - September 2004)
- Bartek J, Lukas C, Lukas J. Checking on DNA damage in S phase. Nat Rev Mol Cell Biol 5: 792-804, 2004.
- Tapias, A et al. Ordered conformational changes in damaged DNA induced by nucleotide excision repair factors. J. Biol. Chem. 279: 19074-19083, 2004.
- Shroff, R. et al. Distribution and dynamics of chromatin modification induced by a defined DNA double-strand break.Curr. Biol. 14: 1703-1711, 2004.
- Jans, J et al. Powerful skin cancer protection by a CPD-photolyase transgene.Curr. Biol. 15: 105-115, 2005.
- Modrich, P. Mechanisms of eukaryotic mismatch repair. J. Biol. Chem. 281: 30305-30309, 2006.
- Sugasawa, K. UV-induced ubiquitylation of XPC complex, the UV-DDB-ubiquitin ligase complex, and DNA repair. J. Mol. Hist. published online; not yet available in printed format, 2006.
- Friedberg, EC. Suffering in silence: the tolerance of DNA damage. Nature Reviews: Mol. Cell. Biol. 6: 943-953, 2006.
- Friedberg EC, Walker GC, Siede W, Wood RD, Schultz RA, Ellenberger T (2006) DNA Repair and Mutagenesis. ASM Press, Washington, DC.
- Weinberg RA (2007) The Biology of Cancer. Garland Science, New York (especially Chapter 12). On reserve in the RPCI library.
The world of DNA repair is far more extensive than covered in the reviews mentioned above. There is a foundation of experimental investigations in the field going back 70 years or more, and there is a plethora of questions under current investigation to which only partial answers are available, to say nothing of the many questions that are raised with each new discovery. Needless to say, in only 2 lectures I cannot possibly provide a satisfactory account of the richness or diversity of the field, or of its experimental foundations. Instead, these lectures are designed with one goal: to provide the student with a superficial understanding of the major repair pathways, as we now understand them. For more detail, I strongly recommend the readings listed above, or other investigations into the current and past literature. In particular, I will not provide any literature citations in these lectures, because there are far too many conclusions that are worthy of citation, and the list of citations that would be generated is far too long.
I also wish to point out that these lectures are focused on the classic DNA repair pathways. In recent years we have developed, and are still developing, an awareness of the importance of the interactions between the classic DNA repair pathways and recombination, replication, transcription, cell cycle checkpoints, chromatin structure, and the cell's constant existential question: is the current state of damage so great that I (the cell) should initiate apoptosis? These extremely interesting topics are, unfortunately, beyond what I can cover in these two lectures (although I'll attempt to touch on some of them). I encourage the reader to use other resources to learn about these topics.