A5079764676- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- DNA and Nucleic Acid Chemistry
- CRISPR and Genetic Engineering
- Bacterial Genetics and Biotechnology
- Molecular Biology Techniques and Applications
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Renal and related cancers
- Genetics and Neurodevelopmental Disorders
- Cell Adhesion Molecules Research
- Cancer therapeutics and mechanisms
- S100 Proteins and Annexins
- Protease and Inhibitor Mechanisms
- Advanced biosensing and bioanalysis techniques
- Cytomegalovirus and herpesvirus research
Vanderbilt University
2008-2024
Helicase-like transcription factor (HLTF) is a central mediator of the DNA damage response and maintains genome stability by regressing stalled replication forks. The N-terminal HIRAN domain binds specifically to 3'-end single-stranded (ssDNA), disrupting this function interferes with fork regression in vitro as well progression cells under stress. Here, we investigated mechanism which HIRAN-ssDNA interaction facilitates remodeling. Our results indicated that capture denatured nascent...
Significance Mutations in SMARCAL1, a DNA remodeling protein fundamental to genome integrity during replication, lead the developmental disorder Schimke immuno-osseous dysplasia (SIOD). SMARCAL1-deficient cells exhibit collapsed replication forks, S-phase cell cycle arrest, increased chromosomal breaks, hypersensitivity genotoxic agents, and instability. SMARCAL1 facilitates restart by catalyzing ATP-dependent fork regression branch migration, mechanism of which is poorly understood. Here we...
Topological stress can cause converging replication forks to stall during termination of vertebrate DNA synthesis. However, ultimately overcome fork stalling, suggesting that alternative mechanisms exist. Using proteomics in Xenopus egg extracts, we show the helicase RTEL1 and replisome protein MCM10 are highly enriched on chromatin convergence crucially important for under conditions topological stress. cooperate promote do not impact topoisomerase activity but progression through a...
The NEIL3 DNA glycosylase maintains genome integrity during replication by excising oxidized bases from single-stranded (ssDNA) and unhooking interstrand cross-links (ICLs) at fork structures. In addition to its N-terminal catalytic domain, contains two tandem C-terminal GRF-type zinc fingers that are absent in the other NEIL paralogs. ssDNA binding GRF-ZF motifs helps recruit forks converged an ICL, but nature of effect domain on catalysis base excision ICL is unknown. Here, we show GRF-ZFs...
Summary G-quadruplexes (G4s) form throughout the genome and influence important cellular processes, but their deregulation can challenge DNA replication fork progression threaten stability. Here, we demonstrate an unexpected, dual role for dsDNA translocase HLTF in G4 metabolism. First, find that is enriched at G4s human suppresses accumulation cell cycle using its ATPase activity. This function of affects telomere maintenance by restricting alternative lengthening telomeres, a process...
Abstract During DNA replication, the replisome encounters obstacles including lesions, transcription-replication conflicts, and other sources of replication stress. These must be efficiently overcome to complete synthesis minimize genome instability. One pathway tolerate stress is fork reversal, in which parental template strands are reannealed a nascent-nascent duplex formed. Several enzymes promote ATP-dependent translocases SMARCAL1, ZRANB3, HLTF. How these translocate on that contains...
ABSTRACT Topological stress can cause replication forks to stall as they converge upon one another during termination of vertebrate DNA synthesis. However, ultimately overcome topological and complete synthesis, suggesting that alternative mechanisms stress. We performed a proteomic analysis converging were stalled by in Xenopus egg extracts. found the helicase RTEL1 replisome protein MCM10 highly enriched on under these conditions. show normally plays minor role fork convergence while is...