Nucleotide excision repair "a legacy of creativity"

被引:31
作者
Cleaver, JE [1 ]
Karplus, K
Kashani-Sabet, M
Limoli, CL
机构
[1] Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Ctr Canc, San Francisco, CA 94143 USA
[3] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA
[4] Univ Calif San Francisco, Melanoma Ctr, San Francisco, CA 94143 USA
[5] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA
来源
MUTATION RESEARCH-DNA REPAIR | 2001年 / 485卷 / 01期
关键词
nucleotide excision repair; xeroderma pigmentosum; ultraviolet light; polymerase eta; recombination; hMre11; p53;
D O I
10.1016/S0921-8777(00)00073-2
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
The first half of the 20th century has seen an enormous growth in our knowledge of DNA repair, in no small part due to the work of Dirk Bootsma, Philip Hanawalt and Bryn Bridges; those honored by this issue. For the new millennium, we have asked three general questions: (A) Do we know all possible strategies of nucleotide excision repair (NER) in all organisms? (B) How is NER integrated and regulated in cells and tissues? (C) Does DNA replication represent a new frontier in the roles of DNA repair? We make some suggestions for the kinds of answers the next generation may provide. The kingdom of archea represents an untapped field for investigation of DNA repair in organisms with extreme lifestyles. NER appears to involve a similar strategy to the other kingdoms of prokaryotes and eukaryotes, but subtle differences suggest that individual components of the system may differ. NER appears to be regulated by several major factors, especially p53 and Rb which interact with transcription coupled repair and global genomic repair, respectively. Examples can be found of major regulatory changes in repair in testicular tissue and melanoma cells. Our understanding of replication of damaged DNA has undergone a revolution in recent years, with the discovery of multiple low-fidelity DNA polymerases that facilitate replicative bypass. A secondary mechanism of replication in the absence of NER or of one or more of these polymerases involves sister chromatid exchange and recombination (hMre11/hRad50/Nbs1). The relative importance of bypass and recombination is determined by the action of p53. We hypothesise that these polymerases may be involved in resolution of complex DNA structures during completion of replication and sister chromatid resolution. With these fascinating problems to investigate, the field of DNA repair will surely not disappoint the next generation. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
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页码:23 / 36
页数:14
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