Evaluation of thrombotic thrombocytopenic purpura and other thrombotic microangiopathies: Lessons learned from a 14-year retrospective study.

Introduction: Thrombotic thrombocytopenic purpura (TTP) is a clinical thrombotic microangiopathy (TMA) syndrome defined by the pentad of symptoms. Therapeutic plasma exchange with plasma replacement is an ASFA Category I modality that can reduce morbidity and mortality if initiated early. We describe a 14-year review of patients referred for plasma exchange with a suspected diagnosis of TTP.

An RNF168 fragment defective for focal accumulation at DNA damage is proficient for inhibition of homologous recombination in BRCA1 deficient cells.

The E3 ubiquitin ligase RNF168 is a DNA damage response (DDR) factor that promotes monoubiquitination of H2A/H2AX at K13/15, facilitates recruitment of other DDR factors (e.g. 53BP1) to DNA damage, and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1.

RING finger nuclear factor RNF168 is important for defects in homologous recombination caused by loss of the breast cancer susceptibility factor BRCA1.

Background: RNF168 promotes chromosomal break localization of 53BP1 and BRCA1; 53BP1 loss rescues homologous recombination (HR) in BRCA1-deficient cells.

Results: RNF168 depletion suppresses HR defects caused by BRCA1 silencing; RNF168 influences HR similarly to 53BP1.

Conclusion: RNF168 is important for HR defects caused by BRCA1 loss.