Nucleic Acids Research, Vol 26, Issue 17 3908-3914, Copyright © 1998 by Oxford University Press
W Xiao, SL Lin, S Broomfield, BL Chow and YF Wei
Eukaryotic genes encoding ubiquitin-congugating enzyme (Ubc)-like proteins
have been isolated from both human and yeast cells. The CROC-1 gene was
isolated by its ability to transactivate c- fos expression in cell culture
through a tandem repeat enhancer sequence. The yeast MMS2 gene was cloned
by its ability to complement the methyl methanesulfonate sensitivity of the
mms2-1 mutant and was later shown to be involved in DNA post-replication
repair. We report here the identification of a human MMS2 ( hMMS2 ) cDNA
encoding a novel human Ubc-like protein. hMMS2 and CROC-1 share >90%
amino acid sequence identity, but their DNA probes hybridize to distinct
transcripts. hMMS2 and CROC-1 also share approximately 50% identity and 75%
similarity with the entire length of yeast Mms2. Unlike CROC-1 , whose
transcript appears to be elevated in all tumor cell lines examined, the
hMMS2 transcript is only elevated in some tumor cell lines. Collectively,
these results indicate that eukaryotic cells may contain a highly conserved
family of Ubc-like proteins that play roles in diverse cellular processes,
ranging from DNA repair to signal transduction and cell differentiation.
The hMMS2 and CROC-1 genes are able to functionally complement the yeast
mms2 defects with regard to sensitivity to DNA damaging agents and
spontaneous mutagenesis. Conversely, both MMS2 and hMMS2 were able to
transactivate a c- fos - CAT reporter gene in Rat-1 cells in a transient
co-transfection assay. We propose that either these proteins function in a
common cellular process, such as DNA repair, or they exert their diverse
biological roles through a similar biochemical interaction relative to
ubiquitination.
ARTICLES
The products of the yeast MMS2 and two human homologs (hMMS2 and CROC- 1) define a structurally and functionally conserved Ubc-like protein family
Department of Microbiology, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada. xiaow@sask.usak.ca
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