A5085087421- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Mitochondrial Function and Pathology
- Metabolism and Genetic Disorders
- Genomics and Chromatin Dynamics
- PARP inhibition in cancer therapy
- RNA modifications and cancer
- Trace Elements in Health
- RNA Research and Splicing
- Carcinogens and Genotoxicity Assessment
- MicroRNA in disease regulation
- Cancer-related molecular mechanisms research
- Genetics and Neurodevelopmental Disorders
- Histone Deacetylase Inhibitors Research
- Ubiquitin and proteasome pathways
- Genetic factors in colorectal cancer
Capital Normal University
2019-2025
Scripps Research Institute
2023-2025
Abstract The reversible post-translational modification (PTM) of proteins plays an important role in many cellular processes. Lysine crotonylation (Kcr) is a newly identified PTM, but its functional significance remains unclear. Here, we found that Kcr involved the replication stress response. We show histone H2A at lysine 119 (H2AK119) and ubiquitination H2AK119 are reversibly regulated by stress. Decrotonylation SIRT1 prerequisite for subsequent BMI1. Accumulation ubiquitinated reversed...
The MRE11/RAD50/NBS1 (MRN) complex plays multiple roles in the maintenance of genome stability. MRN is associated with replication forks to preserve fork integrity and also required for end resection at double-strand breaks (DSBs) facilitate homologous recombination (HR). critical need proper control MRE11 nuclease activity highlighted by extensive nascent strand DNA degradation driven BRCA-deficient cells, leading instability increased sensitivity chemotherapeutics. In this study, we...
Abstract Common fragile sites (CFSs) are regions prone to chromosomal rearrangements, thereby contributing tumorigenesis. Under replication stress (RS), CFSs often harbor under-replicated DNA at the onset of mitosis, triggering homology-directed repair known as mitotic synthesis (MiDAS) complete replication. In this study, we identified an important role mismatch protein MutSβ (MSH2/MSH3) in facilitating MiDAS and maintaining CFS stability. Specifically, demonstrated that is required for...
Abstract The primary role of break-induced replication (BIR) is to repair single-ended double strand breaks (seDSBs) generated at broken forks and eroding telomeres. In this study, we demonstrated that when senataxin (SETX), an RNA/DNA helicase, defective, hyperrecombination using the BIR mechanism induced R-loops/hybrids-accumulated double-ended DNA (deDSBs), suggesting a potential in R-loops/hybrids-associated deDSBs. Intriguingly, while loss SETX initiates non-canonical hyper end...
miRNAs are important regulators of eukaryotic gene expression. The post-transcriptional maturation is controlled by the Drosha-DiGeorge syndrome critical region 8 (DGCR8) microprocessor. Dysregulation miRNA biogenesis has been implicated in pathogenesis human diseases, including cancers. C-terminal–binding protein–interacting protein (CtIP) a well-known DNA repair factor that promotes processing double-strand break (DSB) to initiate homologous recombination–mediated DSB repair. However, it...
Following a DNA double strand break (DSB), several nucleases and helicases coordinate to generate single-stranded (ssDNA) with 3' free ends, facilitating precise repair by homologous recombination (HR). The same can act on stalled replication forks, promoting nascent degradation fork instability. Interestingly, some HR factors, such as CtIP BRCA1, have opposite regulatory effects the two processes, end resection at DSB but inhibiting of forks. However, reason why nuclease actions are...
Break-induced replication (BIR) is mutagenic, and thus its use requires tight regulation, yet the underlying mechanisms remain elusive. Here we uncover an important role of 53BP1 in suppressing BIR after end resection at double strand breaks (DSBs), distinct from protection activity, providing insight into governing regulation DSB repair pathway selection. We demonstrate that loss induces BIR-like hyperrecombination, a manner dependent on Polα-primase-mediated fill-in DNA synthesis...