Rad54 subfamily

The archetype of the Rad54 subfamily is the Rad54 protein from S cerevisiae which was isolated because its inactivation leads to increased sensitivity to ionising radiation. Rad54p and its homologues in other organisms play an important but as yet incompletely understood role in homologous recombination by stimulating Rad51-mediated single strand invasion into the target duplex, and subsequent steps in the process 1, 2.

Many organisms also contain a second subfamily member, such as S cerevisiae Rdh54p or S pombe tid1p. These are frequently implicated in mitotic repair and meiotic crossover 3, although the role of the human homologue RAD54B is unclear 4.

Rad54 proteins have been extensively studied in vitro. They have been shown to be able to generate local changes in DNA topology in supercoiled plasmids 5, 6, 7, to translocate along DNA by biochemical 8 and other methods, and to alter the accessibility of nucleosomal DNA 9, 10, 8. However, this latter activity appears inefficient compared to purified complexes from the Snf2 and Iswi subfamilies.

The crystal structure of the zebrafish Rad54 helicase-like region has recently been determined 11 as described in the structures section.

names associated with subfamily members
Rad54l, hRAD54, RAD54A, Rdh54p, RAD54B, Tid1, okr, okra, mus-25
1: Tan, T. L., R. Kanaar, et al. (2003). Rad54, a Jack of all trades in homologous recombination. DNA Repair (Amst) 2(7): 787-94. PubMed
2: Krogh, B. O. and L. S. Symington (2004). Recombination proteins in yeast. Annu Rev Genet 38: 233-71. PubMed
3: Klein, H. L. (1997). RDH54, a RAD54 homologue in Saccharomyces cerevisiae, is required for mitotic diploid-specific recombination and repair and for meiosis. Genetics 147(4): 1533-43. PubMed
4: Tanaka, K., W. Kagawa, et al. (2002). Human Rad54B is a double-stranded DNA-dependent ATPase and has biochemical properties different from its structural homolog in yeast, Tid1/Rdh54. Nucleic Acids Res 30(6): 1346-53. PubMed
5: Petukhova, G., S. Van Komen, et al. (1999). Yeast Rad54 promotes Rad51-dependent homologous DNA pairing via ATP hydrolysis-driven change in DNA double helix conformation. J Biol Chem 274(41): 29453-62. PubMed
6: Tan, T. L., J. Essers, et al. (1999). Mouse Rad54 affects DNA conformation and DNA-damage-induced Rad51 foci formation. Curr Biol 9(6): 325-8. PubMed
7: Van Komen, S., G. Petukhova, et al. (2000). Superhelicity-driven homologous DNA pairing by yeast recombination factors Rad51 and Rad54. Mol Cell 6(3): 563-72. PubMed
8: Jaskelioff, M., S. Van Komen, et al. (2003). Rad54p is a chromatin remodeling enzyme required for heteroduplex DNA joint formation with chromatin. J Biol Chem 278(11): 9212-8. PubMed
9: Alexiadis, V. and J. T. Kadonaga (2002). Strand pairing by Rad54 and Rad51 is enhanced by chromatin. Genes Dev 16(21): 2767-71. PubMed
10: Alexeev, A., A. Mazin, et al. (2003). Rad54 protein possesses chromatin-remodeling activity stimulated by the Rad51-ssDNA nucleoprotein filament. Nat Struct Biol 10(3): 182-6. PubMed
11: Thoma, N. H., B. K. Czyzewski, et al. (2005). Structure of the SWI2/SNF2 chromatin-remodeling domain of eukaryotic Rad54. Nat Struct Mol Biol 12(4): 350-6. PubMed