A5065147379- DNA Repair Mechanisms
- PARP inhibition in cancer therapy
- CRISPR and Genetic Engineering
- Chromatin Remodeling and Cancer
- Peptidase Inhibition and Analysis
- Genomics and Chromatin Dynamics
- Single-cell and spatial transcriptomics
- Cancer Mechanisms and Therapy
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Genomics and Rare Diseases
- Plant Genetic and Mutation Studies
- Mosquito-borne diseases and control
- Genetic Associations and Epidemiology
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cell death mechanisms and regulation
University of Sussex
2021-2024
Columbia University Irving Medical Center
2024
University of Brighton
2024
Cancer Genetics (United States)
2023
Columbia University
2023
Abstract Poly(ADP-ribose) polymerase 1 (PARP1) is implicated in the detection and processing of unligated Okazaki fragments other DNA replication intermediates, highlighting such structures as potential sources genome breakage induced by PARP inhibition. Here, we show that PARP1 activity greatly elevated chicken human S phase cells which FEN1 nuclease genetically deleted highest behind forks. inhibitor reduces integrity nascent strands both wild-type during replication, does so − / to an...
ABSTRACT High-throughput mutagenesis screens are powerful tools for mapping mutations to phenotypes. However, deciphering the molecular mechanisms that link phenotypic outcomes remains a significant challenge. Here, we present ProTiler-Mut, versatile computational framework harnesses tiling screens, which introduce variants across entire protein sequences, facilitate investigation of mutation-to-phenotype associations at multiple levels, including individual residues, substructures, and...
Summary PARP1&2 enzymatic inhibitors (PARPi) are promising cancer treatments. But recently, their use has been hindered by unexplained severe anemia and treatment-related leukemia. In addition to inhibition, PARPi also trap at DNA lesions. Here, we report that unlike Parp2 -/- mice, which develop normally, mice expressing catalytically-inactive (E534A, EA/EA ) succumb Tp53- Chk2 -dependent erythropoietic failure in utero , mirroring Lig1 mice. While damage mainly activates PARP1,...
Abstract Genomic instability can trigger cancer-intrinsic innate immune responses that promote tumor rejection. However, cancer cells often evade these by overexpressing checkpoint regulators, such as PD-L1. Here, we identify the SNF2-family DNA translocase SMARCAL1 a factor favors evasion dual mechanism involving both suppression of signaling and induction PD-L1-mediated responses. Mechanistically, relieves endogenous damage suppresses cGAS-STING-dependent during cell growth....
Abstract Mammalian DNA replication relies on various helicase and nuclease activities to ensure accurate genetic duplication, but how different are properly directed remains unclear. Here, we identify the ubiquitin-specific protease, USP50, as a chromatin-associated protein required promote ongoing replication, fork restart, telomere maintenance, cellular survival following hydroxyurea or pyridostatin treatment, suppression of breaks near GC-rich sequences. We find that USP50 supports proper...
Abstract PARP1 is implicated in the detection and repair of unligated Okazaki fragment intermediates, highlighting these structures as a potential source genome breakage induced by PARP inhibition. In agreement with this, we show here that activity greatly elevated chicken human S phase cells which FEN1 nuclease genetically deleted, highest tens kilobases behind DNA replication forks. Importantly, inhibitor reduces integrity nascent strands both wild type during replication, does so −/− to...