Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Yang K

PROVIDER: S-EPMC3175720 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Yang Kailin K Moldovan George-Lucian GL Vinciguerra Patrizia P Murai Junko J Takeda Shunichi S D'Andrea Alan D AD

Genes & development 20110901 17

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 ...[more]

PMID: 21896657

Similar Datasets

Project description:Fanconi anemia (FA) pathway is a typical and multienzyme-regulated DNA damage repairer that influences the occurrence and development of disease including cancers. Few comprehensive analyses were reported about the role of FA-related genes (FARGs) and their prognostic values in cancers. In this study, a comprehensive pan-cancer analysis on 79 FARGs was performed. According to the correlation analyses between HPV integration sites and FARGs, we found that FARGs played specific and critical roles in HPV-related cancers, especially in cervical cancer (CC). Based on this, a FARGs-associated prognostic risk score (FPS) model was constructed, and subsequently a nomogram model containing the FPS was developed with a good accuracy for CC overall survival (OS) and recurrence-free survival (RFS) outcome prediction. We also used the similar expression pattern of FARGs by consensus clustering analysis to separate the patients into three subgroups that exhibited significant differential OS but not RFS. Moreover, differential expressed genes (DEGs) between the two risk groups or three clusters were identified and immune pathways as well as cell adhesion processes were determined by functional enrichment analysis. Results indicated that FARGs might promote occurrence and development of CC by regulating the immune cells' infiltration and cell adhesion. In addition, through the machine learning models containing decision tree, random forest, naïve bayes, and support vector machine models, screening of important variables on CC prognosis, we finally determined that ZBTB32 and CENPS were the main elements affecting CC OS, while PALB2 and BRCA2 were for RFS. Kaplan-Meier analysis revealed that bivariate prediction of CC outcome was reliable. Our study systematically analyzed the prognostic prediction values of FARGs and demonstrated their potential mechanism in CC aggressiveness. Results provided perspective in FA pathway-associated modification and theoretical basis for CC clinical treatments.

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets