DNA Repair


The primary structure of DNA is subject to constant change caused by chemical and physical factors. If unchecked, these changes would quickly erode the genetic information. DNA repair mechanisms have evolved to remove potentially deleterious damage and maintain the integrity of the genome in all organisms.

Keywords: DNA repair syndromes; nucleotide excision repair; base excision repair; mismatch repair; recombinational repair

Figure 1.

Molecular model for the incision stage of nucleotide excision repair (NER). In step I, global genome repair (GGR) XPC–hHR23B (C) senses DNA helix‐distorting NER lesions that lead to conformational alterations in the DNA. In transcription‐coupled repair (TCR), lesions are detected by elongating RNA pol that is blocked, for example, by CPDs (NER lesions) and thymine glycols (non‐NER lesion). In step II (left), XPC–hHR23B at the lesion attracts TFIIH, and possibly XPG (G; left). TFIIH creates an opened DNA complex (∼10–20 nt) around the lesion through its helicases XPB and XPD; this step requires ATP. XPC–hHR23B may be released at this or one of the subsequent stages. In step II (right) CSA, CSB, TFIIH, XPG and possibly other cofactors displace the stalled pol II from the lesion, which now becomes accessible for further repair processing; depending on the type of lesion, repair is completed by either NER or other repair pathways. In step III, XPA (A) and RPA stabilize the opening of 10–20 nt and position other factors. XPA binds to the damaged nucleotides and RPA to the undamaged DNA strand. Possibly, RPA binds 8–10 nt, and transition to its 30‐nt binding mode (RPA stretching) may be important in full open complex formation. XPG stabilizes the fully opened complex. In step IV, XPG, positioned by TFIIH and RPA, makes the 3′ incision. ERCC1–XPF (F), positioned by RPA and XPA, makes the second incision 5′ of the lesion. In step V, dual incision is followed by gap‐filling DNA synthesis and ligation. Drawn contacts between molecules reflect reported protein–protein interactions. (Reproduced with permission from de Laat and Jaspers .)



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Further Reading

Balajee AS and Bohr VA (2000) Genomic heterogeneity of nucleotide excision repair. Gene 250(1–2): 15–30.

Chu G and L Mayne (1996) Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy: do the genes explain the diseases? Trends in Genetics 12(5): 187–192.

Hoeijmakers JH (1993) Nucleotide excision repair. I: from E. coli to yeast. Trends in Genetics 9(5): 173–177.

Hoeijmakers JH (1993) Nucleotide excision repair. II: from yeast to mammals. Trends in Genetics 9(6): 211–217.

Hoeijmakers JH (2001) Genome maintenance mechanisms for preventing cancer. Nature 411(6835): 366–374.

Kanaar R and Hoeijmakers JH (1998) Molecular mechanisms of DNA double strand break repair. Trends in Cell Biology 8(12): 483–489.

Web Links

DNA Repair Interest Group http://tango01.cit.nih.gov/sig/home.taf?_function=main&SIG Info_SIGID=32

Human DNA Repair Genes http://www.cgal.icnet.uk/DNA_Repair_Genes.html

Cockayne syndrome 1 (CKN1). LocusID: 10256. Locus Link: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=10256

Excision repair cross‐complementing rodent repair deficiency, complementation group 6 (ERCC6). LocusID: 2074. Locus Link: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=2074

Polymerase (DNA directed), eta (POLH). LocusID: 5429. Locus Link: http://www.ncbi.nlm.nih.gov/LocusLink/LocRpt.cgi?l=5429

Cockayne syndrome 1 (CKN1). MIM number: 216400. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?216400

Excision repair cross‐complementing rodent repair deficiency, complementation group 6 (ERCC6). MIM number: 133540. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?133540

Polymerase (DNA directed), eta (POLH). MIM number: 603968. OMIM: http://www.ncbi.nlm.nih.gov/htbin‐post/Omim/dispmim?603968

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How to Cite close
Reed, Simon Huw, and Waters, Raymond(Sep 2005) DNA Repair. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1038/npg.els.0005284]