Publications by authors named "Sarina Porcella"
Article Synopsis
- - NHEJ and HR are key DNA repair methods for double-strand breaks, with MMEJ serving as a backup; recent research highlights important roles for the 9-1-1 complex and RHINO in MMEJ.
- - RHINO, which accumulates during mitosis and is phosphorylated by PLK1, plays a crucial role in guiding polymerase θ to double-strand breaks for repair.
- - The study shows that MMEJ can repair lingering double-strand breaks from S phase during mitosis, suggesting a complex interaction with PARP inhibitors and a synthetic lethal relationship between certain genes and repair pathways.
DNA double-strand breaks (DSBs) are toxic lesions that can lead to genome instability if not properly repaired. Breaks incurred in G1 phase of the cell cycle are predominantly fixed by non-homologous end-joining (NHEJ), while homologous recombination (HR) is the primary repair pathway in S and G2. Microhomology-mediated end-joining (MMEJ) is intrinsically error-prone and considered a backup DSB repair pathway that becomes essential when HR and NHEJ are compromised.
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- - PDAC (pancreatic ductal adenocarcinoma) often shows mutations in repair proteins, affecting 20%-25% of cases, which results in a vulnerability to certain cancer treatments but also leads to therapy resistance in many patients.
- - The enzyme polymerase theta (POLQ) helps repair DNA through a process called microhomology-mediated end-joining and is overexpressed when homologous recombination processes are inactive, which is common in PDAC cases with mutations in BRCA1 and BRCA2.
- - In studies, knocking down POLQ proved to be synthetically lethal in HR-deficient PDAC models, promoting immune responses and enhancing infiltration of CD8+ T cells, indicating POLQ's
During eukaryotic DNA replication, DNA polymerase alpha/primase (Pol α) initiates synthesis on both the leading and lagging strands. It is unknown whether leading- and lagging-strand priming are mechanistically identical, and whether Pol α associates processively or distributively with the replisome. Here, we titrate cellular levels of Pol α in S.
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