E3 ubiquitin-protein ligase RFWD3

Definition:

E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage. Plays a key role in RPA-mediated DNA damage signaling and repair. Acts by mediating ubiquitination of the RPA complex (RPA1, RPA2 and RPA3 subunits) and RAD51 at stalled replication forks, leading to remove them from DNA damage sites and promote homologous recombination. Also mediates the ubiquitination of p53/TP53 in the late response to DNA damage, and acts as a positive regulator of p53/TP53 stability, thereby regulating the G1/S DNA damage checkpoint. May act by catalyzing the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome. In response to ionizing radiation, interacts with MDM2 and enhances p53/TP53 ubiquitination, possibly by restricting MDM2 from extending polyubiquitin chains on ubiquitinated p53/TP53.

References:

[1]. Zihua Gong, et al. E3 ligase RFWD3 participates in replication checkpoint control. J Biol Chem. 2011 Jun 24;286(25):22308-13. [Content Brief]

[2]. Kerstin Knies, et al. Biallelic mutations in the ubiquitin ligase RFWD3 cause Fanconi anemia. J Clin Invest. 2017 Aug 1;127(8):3013-3027. [Content Brief]

[3]. Andrew E H Elia, et al. RFWD3-Dependent Ubiquitination of RPA Regulates Repair at Stalled Replication Forks. Mol Cell. 2015 Oct 15;60(2):280-93. [Content Brief]

[4]. Laura Feeney, et al. RPA-Mediated Recruitment of the E3 Ligase RFWD3 Is Vital for Interstrand Crosslink Repair and Human Health. Mol Cell. 2017 Jun 1;66(5):610-621.e4. [Content Brief]

[5]. Xiaoyong Fu, et al. RFWD3-Mdm2 ubiquitin ligase complex positively regulates p53 stability in response to DNA damage. Proc Natl Acad Sci U S A. 2010 Mar 9;107(10):4579-84. [Content Brief]

[6]. Shojiro Inano, et al. RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination. Mol Cell. 2017 Jun 1;66(5):622-634.e8. [Content Brief]

[7]. Shangfeng Liu, et al. RING finger and WD repeat domain 3 (RFWD3) associates with replication protein A (RPA) and facilitates RPA-mediated DNA damage response. J Biol Chem. 2011 Jun 24;286(25):22314-22. [Content Brief]

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