Standard Article

You have free access to this content

DNA Repair

  1. Simon Huw Reed,
  2. Raymond Waters

Published Online: 23 SEP 2005

DOI: 10.1038/npg.els.0005284

eLS

eLS

How to Cite

Reed, S. H. and Waters, R. 2005. DNA Repair. eLS. .

Author Information

  1. University of Wales College of Medicine, Cardiff, UK

Publication History

  1. Published Online: 23 SEP 2005
thumbnail image

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 1999.)