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. 2000 Sep;157(3):693-701.
doi: 10.1016/s0002-9440(10)64581-6.

Rous-Whipple Award Lecture. Nucleotide excision repair and cancer predisposition: A journey from man to yeast to mice

E C Friedberg  1
Affiliations

Rous-Whipple Award Lecture. Nucleotide excision repair and cancer predisposition: A journey from man to yeast to mice

E C Friedberg. Am J Pathol. 2000 Sep.
No abstract available

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Figures

Figure 1.
Figure 1.
When cells suffer DNA damage they undergo various responses. These include cell cycle checkpoint activation and/or apoptosis, various modes of DNA repair, various modes of DNA damage tolerance, and the transcriptional activation of multiple genes, some of which are involved in stress responses.
Figure 2.
Figure 2.
When cells in G1 or G2 of the cell cycle are exposed to UV radiation and incubated in the presence of [3H] thymidine, repair synthesis of DNA associated with nucleotide excision repair is reflected by autoradiographic labeling of the nuclei.
Figure 3.
Figure 3.
XP cells from genetic complementation group D (XP-D) are much more sensitive to killing by UV radiation than normal human cells.
Figure 4.
Figure 4.
Yeast rad3 mutants are highly sensitive to UV radiation. However, when such cells are transfected with plasmids containing the RAD3 gene (rad3/pRAD3) UV radiation sensitivity is restored to that observed with wild-type cells (RAD3).
Figure 5.
Figure 5.
The yeast nucleotide excision repairosome is comprised of at least 19 polypeptides, most of which are represented by highly conserved homologous proteins in human cells. The seven proteins represented in red are the subunits of the RNA polymerase II basal transcription factor TFIIH.
Figure 6.
Figure 6.
Schematic representation of nucleotide excision repair in yeast. A: Both the RNAPII transcription initiation complex (green) and the nucleosome (pink) assembled and bound at a site of base damage (triangle) include TFIIH (orange). The Rad3 and Ssl2 DNA helicases unwind a short stretch of DNA during both transcription initiation (left) and NER (right). B: In the case of NER, the unwinding of DNA generates junctions between double- and single-stranded DNA. These junctions are attacked by specific endonucleases such that the Rad2 junction-specific endonuclease cuts the damaged DNA strand 3′ to the site of base damage and the Rad1/Rad10 endonuclease cuts the damaged strand 5′ to this site. C: Following bimodal incision of the damaged strand, the Rad7 and Rad16 proteins somehow facilitate displacement of the resulting oligonucleotide fragment. DNA polymerase δ or ε, together with accessory proteins for DNA replication (RPA, RFC, and PCNA) fill in the gap generated by oligonucleotide excision. DNA ligation completes NER.
Figure 7.
Figure 7.
When mice that are homozygously defective in the Xpc gene (−/−) are exposed to weekly doses of UVB radiation, they develop skin cancers on the shaved dorsal skin more quickly than Xpc wild-type (+/+) or heterozygous (+/−) littermates.
Figure 8.
Figure 8.
The kinetics of skin cancer induction in mice indicate that whereas irradiated Xpc−/− animals develop skin cancers very quickly, in time heterozygous mutant (+/−) mice develop skin cancers more rapidly than wild-type (+/+) animals. Circles, Xpc−/− mice; triangles, Xpc+/+ mice; squares, Xpc+/− mice.
See this image and copyright information in PMC

References

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