Double-strand break repair pathways

Riha K, Heacock ML, Shippen DE. The role of the nonhomologous end-joining DNA double-strand break repair pathway in telomere biology. Annu. Rev. Genet. 2006 40 237-277. 

Shrivastav, M., De Haro, L.P., Nickoloff, J.A. 2008. Regulation of DNA double-strand break repair pathway choice. Cell Res 18(1) 134—147. 

Richardson C, Stark JM, Ommundsen M et al (2004) Rad51 overexpression promotes alternative double-strand break repair pathways and genome instability. Oncogene 23 546-553... 

In this double-strand break repair model for recombination, the 3 ends are used to initiate the genetic exchange. Once paired with the complementary strand on the intact homolog, a region of hybrid DNA is created that contains complementary strands from two different parent DNAs (the product of step (2)in Fig. 25-31a). Each of the 3 ends can then act as a primer for DNA replication. The structures thus formed, Holliday intermediates (Fig. 25 31b), are a feature of homologous genetic recombination pathways in all organisms. 

Takata M, Sasaki MS, Sonoda E, Morrison C, Hashimoto M, Utsumi H, Yamaguchi-Iwai Y, Shinohara A, Takeda S. Homologous recombination and non-homologous end-joining pathways of DNA double-strand break repair have overlapping roles in the maintenance of chromosomal integrity in vertebrate cells. EMBO J. 1998 17 5497-5508. 

Rothkamm K, Lobrich M (2003) Evidence for a lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Natl Acad Sci USA 100 5057-5062 Rothkamm K, Kruger I, Thompson LH et al (2003) Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol 23 5706-5715 Riibe C, Dong X, Kiihne M et al (2008) DNA double-strand rejoining in complex normal tissues. Int J Radiat Biol Relat Stud Phys Chem Med 72 1180-1187 Ruiz de Almodovar JM, Nunez MI, McMillan TJ et al (1994) Initial radiation-induced DNA damage in human tumour cell lines a correlation with intrinsic cellular radiosensitivity. Br J Cancer 69 457-462... 

Ross WE, Glaubiger DL, Kohn KW (1978) Protein-associated DNA breaks in cells treated with adriamycin or elhpticine. Biochim Biophys Acta 519(l) 23-30 Rothfuss A, Grompe M (2004) Repair kinetics of genomic interstrand DNA cross-hnks evidence for DNA double-strand break-dependent activation of the Fanconi anemia/BRCA pathway. Mol Cell Biol 24(1) 123-134... 

FIGURE 25-37 Models for recombinational DNA repair of stalled replication forks. The replication fork collapses on encountering a DNA lesion (left) or strand break (right). Recombination enzymes promote the DNA strand transfers needed to repair the branched DNA structure at the replication fork. A lesion in a single-strand gap is repaired in a reaction requiring the RecF, RecO, and RecR proteins. Double-strand breaks are repaired in a pathway requiring the RecBCD enzyme. Both pathways require RecA. Recombination intermediates... 

HR is important for the rescue of collapsed replication forks. NHEJ is the physiological recombination mechanism in V(D)J recombination and seems to be the major pathway of the repair of double-stranded breaks induced by ionizing radiation and radiomimetic agents in mammals. 

Wang M, Wu W, Wu W, Rosidi B, Zhang L, Wang H, Bi-akis G. PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways. Nucleic Acids Res. 2006 34 6170-6182. 

Repair of double-strand breaks by the end-joining pathway can link segments of DNA from different chromosomes, possibly forming an oncogenic translocation. The repair mechanism also produces a small deletion, even when segments from the same chromosome are joined. 

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