RFWD3

RFWD3 (Ring Finger And WD Repeat Domain 3) is a Protein Coding gene. Diseases associated with RFWD3 include Fanconi Anemia, Complementation Group W and Fanconi Anemia, Complementation Group A. Gene Ontology (GO) annotations related to this gene include ligase activity and p53 binding.

ring finger and WD repeat domain 3

E3 ubiquitin-protein ligase required for the repair of DNA interstrand cross-links (ICL) in response to DNA damage (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575657, PubMed:28575658).
Plays a key role in RPA-mediated DNA damage signaling and repair (PubMed:21504906, PubMed:21558276, PubMed:26474068, PubMed:28575657, PubMed:28575658, PubMed:28691929).
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 (PubMed:26474068, PubMed:28575657, PubMed:28575658).
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 (PubMed:20173098).
May act by catalyzing the formation of short polyubiquitin chains on p53/TP53 that are not targeted to the proteasome (PubMed:20173098).
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 (PubMed:20173098).

Biological Process cellular response to DNA damage stimulusManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process double-strand break repair via homologous recombinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process interstrand cross-link repairManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process mitotic G1 DNA damage checkpoint signalingManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process protein ubiquitinationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process regulation of DNA damage checkpointManual Assertion Based On ExperimentIMP:UniProtKB
Biological Process replication fork processingManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process response to ionizing radiationManual Assertion Based On ExperimentIDA:UniProtKB

Nucleus
Nucleus, PML body
Cytoplasm
In undamaged cells, found both in the cytoplasm and in the nucleus, partially associated with PML nuclear bodies (PubMed:21558276).
In response to replication block, such as that caused by hydroxyurea treatment, or to DNA damage caused by ionizing radiations or doxorubicin, recruited to the nucleus, to stalled replication forks or to sites of DNA repair (PubMed:21504906, PubMed:28575657).
This recruitment depends upon RPA2 (PubMed:21504906).

Fanconi anemia, complementation group W (FANCW):
A form of Fanconi anemia, a disorder affecting all bone marrow elements and resulting in anemia, leukopenia and thrombopenia. It is associated with cardiac, renal and limb malformations, dermal pigmentary changes, and a predisposition to the development of malignancies. At the cellular level it is associated with hypersensitivity to DNA-damaging agents, chromosomal instability (increased chromosome breakage) and defective DNA repair.