Rad5/16 subfamily

The archetypes of this subfamily are the S cerevisiae Rad5 and Rad16 proteins. Both are intimately involved in DNA repair pathways:

Rad5p acts via its RING finger with the Ubc13p-Mms2p E2 ligase complex to poly-ubiquitylate PCNA in one fate of the Rad6 pathway of replication linked DNA damage bypass 1. It has also been suggested that Rad5p participates in double-stranded break repair in a role dependent on its helicase-like region but not its RING finger 2. A clear function for the helicase-like motor in either role has not been suggested.

Rad16p acts in complex with Rad7p and Elc1p as the NEF4 nucleotide excision repair factor 3, 4, possibly scanning along chromatin for lesions as part of non-transcribed strand repair 3 or by distorting DNA to expose the lesion for processing 5. Although the basis is not known, the RING finger influences the stability of the Rad4 protein responsible for recognising the lesion 4.

Paradoxically, no DNA repair link has been reported for the single member of the Rad5/16 subfamily present in each mammalian genome (e.g. human SMARCA3). No functional role has been attributed to the RING finger.

Instead, under the name RUSH1alpha the mammalian Rad5/16 subfamily members have been reported to act as steroid regulated transcriptional regulators 6, and the same gene (referred to as HLTF) has been observed to be silenced in a number of cancers 7.

names associated with subfamily members
rhp16, rad8, SMARCA3, SNF2L3, HIP116, HLTF, ZBU1, RNF80, RUSH-1alpha, P113, MUG13.1
1: Hoege, C., B. Pfander, et al. (2002). RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419(6903): 135-41. PubMed
2: Chen, S., A. A. Davies, et al. (2005). The RING finger ATPase Rad5p of Saccharomyces cerevisiae contributes to DNA double-strand break repair in a ubiquitin-independent manner. Nucleic Acids Res 33(18): 5878-86. PubMed
3: Guzder, S. N., P. Sung, et al. (1998). The DNA-dependent ATPase activity of yeast nucleotide excision repair factor 4 and its role in DNA damage recognition. J Biol Chem 273(11): 6292-6. PubMed
4: Ramsey, K. L., J. J. Smith, et al. (2004). The NEF4 complex regulates Rad4 levels and utilizes Snf2/Swi2-related ATPase activity for nucleotide excision repair. Mol Cell Biol 24(14): 6362-78. PubMed
5: Yu, S., T. Owen-Hughes, et al. (2004). The yeast Rad7/Rad16/Abf1 complex generates superhelical torsion in DNA that is required for nucleotide excision repair. DNA Repair (Amst) 3(3): 277-87. PubMed
6: Hewetson, A., E. C. Hendrix, et al. (2002). Identification of the RUSH consensus-binding site by cyclic amplification and selection of targets: demonstration that RUSH mediates the ability of prolactin to augment progesterone-dependent gene expression. Mol Endocrinol 16(9): 2101-12. PubMed
7: Moinova, H. R., W. D. Chen, et al. (2002). HLTF gene silencing in human colon cancer. Proc Natl Acad Sci U S A 99(7): 4562-7. PubMed