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
references
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
