A5036536501- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- Carcinogens and Genotoxicity Assessment
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Epigenetics and DNA Methylation
- CRISPR and Genetic Engineering
Indiana University Bloomington
2021-2025
Abstract Translesion synthesis (TLS) employs specialized polymerases to incorporate nucleotides opposite DNA lesions, allowing replication continue temporarily without repairing the while sacrificing fidelity ( 1 ). TLS depends on a ubiquitin molecule attached clamp PCNA at residue Lys 164 2, 3 ); precise biochemical and molecular basis how modification stimulates is still elusive 4-10 In this study, we discovered that polymerase δ (Pol δ) 3’ 5’ “proofreading” exonuclease degrades nascent...
Abstract The yeast protein Rad5 and its orthologs in other eukaryotes promote replication stress tolerance cell survival using their multiple activities, including ubiquitin ligase, fork remodeling DNA lesion targeting activities. Here, we present the crystal structure of a nearly full-length protein. shows three distinct, but well-connected, domains required for Rad5’s spatial arrangement these suggest that different can have autonomous activities also undergo intrinsic coordination....
DNA repair dysregulation is a key driver of cancer development. Understanding the molecular mechanisms underlying in cells crucial for development and therapies. Here, we report that enhancer zeste homolog 2 (EZH2) directly methylates poly(adenosine diphosphate–ribose) polymerase-1 (PARP-1), an essential enzyme involved repair, regulates its activity. Functionally, EZH2-catalyzed methylation represses PARP1 catalytic activity, down-regulates recruitment x-ray cross-complementing group-1 to...