Double-strand break repair

Figure 36-25. Double-strand break repair of DNA. The proteins Ku and DNA-dependent protein kinase combine to approximate the two strands and unwind them. The aligned fragments form base pairs the extra ends are removed, probably by a DNA-PK-associated endo- or exonuclease, and the gaps are filled in and continuity is restored by ligation.

Hopfner, K. P., Karcher, A., Shin, D. S., Craig, L., Arthur, L. M., Carney, J. P. and Tainer, J. A. (2000). Structural biology of Rad50 ATPase ATP-driven conformational control in DNA double-strand break repair and the ABC-ATPase superfamily, Cell, 101, 789-800. 

Hendrickson, E.A., 1997, CeU-cycle regulation ofmammalian DNA double-strand-break repair, Am.J.Hum.Genet. 61 795-800. 

Chowdhury D, Keogh MC, Ishii H, Peterson CL, Buratowski S, Lieberman J (2005) gamma-H2AX dephosphorylation by protein phosphatase 2A facilitates DNA double-strand break repair. Mol Cell 20 801-809. 

Wei Y, Yu L, Bowen J, Gorovsky MA, Allis CD (1999) Phosphorylation of histone H3 is required for proper chromosome condensation and segregation. Cell 97(1) 99—109 Wyatt HR, Liaw H, Green GR, Lustig AJ (2003) Multiple roles for Saccharomyces cerevisiae histone H2A in telomere position effect, Spt phenotypes and double-strand-break repair. Genetics 164(l) 47-64... 

Wiltshire TD, Lovejoy CA, WangT et al (2010) Sensitivity to polyADP-ribose polymerase PARP inhibition identifies ubiquitin-specific peptidase 11 USPll as a regulator of DNA double-strand break repair. J Biol Chem 285 14565-14571... 

Boubnov NV, Hall KT, Wills Z, et al. Complementation of the ionizing radiation sensitivity, DNA end binding, and V(D)J recombination defects of double-strand break repair mutants by the p86 Ku autoantigen. Proc Natl Acad Sci USA 1995 92(3) 890-894. 

Bruso CE, Shewach DS, Lawrence TS. Fluorodeoxyuridine-induced radiosensitization and inhibition of DNA double strand break repair in human colon cancer cells. Int J Radiat Oncol Biol Phys 1990 19 1411-1417. 

Nlbrln, a novel DNA double-strand break repair protein, Is mutated In Nijmegen breakage syndrome... 

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. 

DNA transposition 978 meiosis 979 branch migration 980 double-strand break repair model 980 Holliday intermediate 980... 

Gene A, allele a with intron double-strand break repair... 

Biedermann, K.A., Sun, J., Giaccia, A.J., Tosto, L.M., Brown, J.M. (1991). scid mutation in mice confers hypersensitivity to ionizing radiation and a deficiency in ONA double-strand break repair. Proc. Natl. Acad. Sci. USA 88,1394-1397. 

Rashid R, Langfinger D, Wagner R, Schuchmann H-P, von Sonntag C (1999) Bleomycin vs. OH-radi-cal-induced malonaldehydic-product formation in DNA. Int J Radiat Biol 75 110-109 Rothkamm K, Lobrich M (2003) Evidence for the lack of DNA double-strand break repair in human cells exposed to very low x-ray doses. Proc Nat Acad Sci USA 100 5057-5082 Sapora O, Fielden EM, LoverockPS (1975) The application of rapid lysis techniques in radiobiology. I. The effect of oxygen and radiosensitizers on DNA strand break production and repair in E. coli B/r. Radiat Res 64 431-442... 

Figure 23.14. A general model for double-strand break repair using homologous recombination. The text in parentheses to the right indicates proteins that participate in each step in E. coli. The light blue lines indicate newly synthesized DNA. (Reproduced with permission from Kowalczykowski, S.C. Initiation of genetic recombination and recombination-dependent replication. Trends Biochem. Sci. 25 156-165, 2000.) See color insert.

Double-Strand Break Repair in Eukaryotic Cells... 

Hanakahi, L.A., Bartlet-Jones, M., Chappell, C., and West, S.C., 2000, Binding of inositol phosphate to DNA-PK and stimulation of double-strand break repair. Cell 102 721-729... 

Kanaar R, Hoeijmakers JH, van Gent DC. (1998) Molecular mechanisms of DNA double strand break repair. Trends Cell Biol 8 483-489. 

Valerie K, Povirk LF. Regulation and mechanisms of mammalian double-strand break repair. Oncogene 2003 22 5792-5812. 

Double-Strand Break Repair and Recombina-tional Repair)... 

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