Replication Fork Stability Confers Chemoresistance in BRCA-deficient Cells

Brca1- and Brca2-deficient cells have reduced capacity to repair DNA double-strand breaks (DSBs) by homologous recombination (HR) and consequently are hypersensitive to DNA damaging agents, including cisplatin and poly(ADP-ribose) polymerase (PARP) inhibitors. Here we show that loss of the MLL3/4 complex protein, PTIP, protects Brca1/2-deficient cells from DNA damage and rescues the lethality of Brca2-deficient embryonic stem cells. However, PTIP deficiency does not restore HR activity at DSBs. Instead, its absence inhibits the recruitment of the MRE11 nuclease to stalled replication forks, which in turn protects nascent DNA strands from extensive degradation. More generally, acquisition of PARPi and cisplatin resistance is associated with replication fork (RF) protection in Brca2-deficient tumor cells that do not develop Brca2 reversion mutations. Disruption of multiple proteins, including PARP1 and CHD4, leads to the same end point of RF protection, highlighting the complexities by which tumor cells evade chemotherapeutic interventions and acquire drug resistance

Depressive and Anxiety Symptoms and Their Relationships with Ego-Resiliency and Life Satisfaction among Well-Educated, Young Polish Citizens during the COVID-19 Pandemic

Ego-resiliency is a set of traits that promotes positive adaptation to life’s vicissitudes. High ego-resiliency helps in upholding one’s personality system when facing adversity and in adjusting it to new environmental demands. Our study aimed at evaluating the connections between ego-resiliency, the severity of anxiety and depressive symptoms as well as life satisfaction during the COVID-19 pandemic in Poland. A total of 604 Polish citizens aged 16 to 69 years participated in the online survey. Ego-resiliency was measured with the Ego Resiliency Scale (ER89-R12), anxiety and depression with the Hospital Anxiety and Depression Scale (HADS), and life satisfaction with the Satisfaction with Life Scale (SWLS). Statistical analyses were performed using the Spearman rank correlation coefficient. The results revealed correlations between the intensity of depressive and anxiety symptoms, life satisfaction, and the intensity of ego-resiliency. Individuals with a high level of ego-resiliency tended to experience a lower intensity of anxiety and depressive symptoms during the COVID-19 pandemic. Moreover, individuals with a high level of ego-resiliency exhibited a higher level of life satisfaction. Our conclusions might assist in better understanding the close link between levels of ego-resiliency, the occurrence of depressive and anxiety symptoms, and satisfaction with life among Polish individuals experiencing crises