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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Bermudez, Vladimir Unk, Ildiko Hajdú, Ildikó Prakash, Satya Hurwitz, Jerard Haracska, Lajos Fátyol, Károly Prakash, Louise Szakál, Barnabás Blastyák, András |
| Description | Author Affiliation: Unk I ( Institute of Genetics, Biological Research Center, Hungarian Academy of Sciences, H-6726 Szeged, Hungary.); |
| Abstract | Human SHPRH gene is located at the 6q24 chromosomal region, and loss of heterozygosity in this region is seen in a wide variety of cancers. SHPRH is a member of the SWI/SNF family of ATPases/helicases, and it possesses a C(3)HC(4) RING motif characteristic of ubiquitin ligase proteins. In both of these features, SHPRH resembles the yeast Rad5 protein, which, together with Mms2-Ubc13, promotes replication through DNA lesions via an error-free postreplicational repair pathway. Genetic evidence in yeast has indicated a role for Rad5 as a ubiquitin ligase in mediating the Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Here we show that SHPRH is a functional homolog of Rad5. Similar to Rad5, SHPRH physically interacts with the Rad6-Rad18 and Mms2-Ubc13 complexes, and we show that SHPRH protein is a ubiquitin ligase indispensable for Mms2-Ubc13-dependent polyubiquitylation of proliferating cell nuclear antigen. Based on these observations, we predict a role for SHPRH in promoting error-free replication through DNA lesions. Such a role for SHPRH is consistent with the observation that this gene is mutated in a number of cancer cell lines, including those from melanomas and ovarian cancers, which raises the strong possibility that SHPRH function is an important deterrent to mutagenesis and carcinogenesis in humans. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 48 |
| Volume Number | 103 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2006-11-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | DNA Helicases Metabolism Proliferating Cell Nuclear Antigen Ubiquitin-Conjugating Enzymes Ubiquitin-Protein Ligases Ubiquitin Adenosine Triphosphatases Chemistry Amino Acid Sequence Cell Line DNA Genetics Isolation & Purification Molecular Sequence Data Protein Binding Saccharomyces Cerevisiae Enzymology Saccharomyces Cerevisiae Proteins Sequence Alignment Sequence Homology, Amino Acid Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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