Searching across hundreds of databases

Our searching services are busy right now. Your search will reload in five seconds.

Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Regulation of the Fanconi anemia pathway by a SUMO-like delivery network.

Genes & development | Sep 1, 2011

The USP1/UAF1 complex deubiquitinates the Fanconi anemia protein FANCD2, thereby promoting homologous recombination and DNA cross-link repair. How USP1/UAF1 is targeted to the FANCD2/FANCI heterodimer has remained unknown. Here we show that UAF1 contains a tandem repeat of SUMO-like domains in its C terminus (SLD1 and SLD2). SLD2 binds directly to a SUMO-like domain-interacting motif (SIM) on FANCI. Deletion of the SLD2 sequence of UAF1 or mutation of the SIM on FANCI disrupts UAF1/FANCI binding and inhibits FANCD2 deubiquitination and DNA repair. The USP1/UAF1 complex also deubiquitinates PCNA-Ub, and deubiquitination requires the PCNA-binding protein hELG1. The SLD2 sequence of UAF1 binds to a SIM on hELG1, thus targeting the USP1/UAF1 complex to its PCNA-Ub substrate. We propose that the regulated targeting of USP1/UAF1 to its DNA repair substrates, FANCD2-Ub and PCNA-Ub, by SLD-SIM interactions coordinates homologous recombination and translesion DNA synthesis.

Pubmed ID: 21896657 RIS Download

Mesh terms: Adenosine Triphosphatases | Amino Acid Sequence | Animals | Arabidopsis Proteins | Cell Line | Chickens | DNA-Binding Proteins | Endopeptidases | Fanconi Anemia Complementation Group Proteins | Gene Expression Regulation | Gene Knockdown Techniques | HeLa Cells | Humans | Models, Molecular | Nuclear Proteins | Proliferating Cell Nuclear Antigen | Protein Binding | Protein Structure, Tertiary | Recombination, Genetic | Small Ubiquitin-Related Modifier Proteins | Tandem Repeat Sequences | Ubiquitin | Ubiquitin-Specific Proteases

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

We have not found any resources mentioned in this publication.