Nucleotide damage recognition

Hartman AR, Ford JM. BRCAl induces DNA damage recognition factors and enhances nucleotide excision repair. Nat Genet 2002 32 180-184. 

Damage recognition by the nucleotide excision repair multiprotein complex. 

Figure 6 Nucleotide excision repair in (A) E. coli and (B) humans. There are five basic steps of nucieotide excision repair (1) damage recognition, (2) dual incisions, (3) release of the excised oligomer, (4) repair synthesis to fill in the gap, and (5) ligation.

Uvr A, a damage recognition protein, detects helical distortion caused by DNA adducts such as thymine dimers (a). It then associates with Uvr B to form the A2B complex. After binding to the damaged segments, A2B forces DNA to bend. Uvr A then dissociates (b). The binding of the nuclease Uvr C to Uvr B (c) and the action of the helicase Uvr D (d) results in the excision of a 12-nucleotide DNA strand (12-mer). After Uvr B is released (e) the excision gap is repaired by pol I (f). 

Dip, R., Camenisch, U., and Naegeli, H. (2004) Mechanisms of DNA damage recognition and strand disdimination in human nucleotide exdsion repair. DNA Repair, 2,1409-1423. 

Y., Masutani, C., Iwai, S., and Hanaoka, F. (2001) A multistep damage recognition mechanism for global genomic nucleotide excision repair. Genes Dev., 15, 507-521. 

Wood, R.D. (1999) DNA damage recognition during nucleotide excision repair in mammalian cells. Biochimie, 81, 39-44. 

Batty, D., and R. Wood. 2000. Damage recognition in nucleotide excision repair of DNA. Gene 241 193-204. 

Xeroderma pigmentation (XP) is an autosomal recessive human disease charactenzed by hypersensitivity to sunlight and a high incidence of skin cancer in sun-exposed area. XPA is a monomeric 31 kDa DNA-binding protem known to be involved in the damage recognition step of nucleotide excision repair processes. 

Fig. 1. Schematic illustration of nucleotide excision repair in prokaryotes and eukaryotes. The basic steps are conserved damage recognition and dual incisions to excise DNA damage, helicase activity to displace excised oligomer and repair factors, and resynthesis/ligation to restore the integrity of the DNA molecule. (See Color Insert.)...

R461 K. Morikawa and M. Shirikawa, Three-Dimensional Structural View of Damaged-DMA Recognition T4 Endonuclease V, E. coli Vsr, Protein, and Human Nucleotide Excision Repair Factor XPA , Mutat. Res., 2000,460, 257... 

Min, J.H. and Pavletich, N.P. (2007) Recognition of DNA damage by the Rad4 nucleotide excision repair protein. Nature, 449, 570-575. 

The negative selective pressure imposed by lesion nucleobases has driven the evolution of repair pathways dedicated to recognition and removal of base lesions, followed by restoration of the original DNA sequence-(Lindahl, 1993). The major pathway for this type of repair (Fig. 1) is initiated by the excision of a damaged base and is therefore known as base excision DNA repair (BER). Another repair pathway, nucleotide excision repair (NER), can also repair some lesion nucleobases that severely distort the DNA helix. The NER pathway is discussed in Chapter 2. 

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