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

Genes & development | Sep 1, 2011

http://www.ncbi.nlm.nih.gov/pubmed/21896657

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

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