A5073895573- DNA Repair Mechanisms
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Ubiquitin and proteasome pathways
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- RNA modifications and cancer
- Cancer-related molecular mechanisms research
- CRISPR and Genetic Engineering
- Cancer therapeutics and mechanisms
- Glycosylation and Glycoproteins Research
- PARP inhibition in cancer therapy
- MicroRNA in disease regulation
- Cancer Genomics and Diagnostics
- Advanced Breast Cancer Therapies
- Histone Deacetylase Inhibitors Research
- Chronic Lymphocytic Leukemia Research
- Chromosomal and Genetic Variations
- DNA and Nucleic Acid Chemistry
- Ovarian cancer diagnosis and treatment
- Carcinogens and Genotoxicity Assessment
- Ferroptosis and cancer prognosis
- Cytokine Signaling Pathways and Interactions
- RNA Research and Splicing
- Immune Cell Function and Interaction
George Washington University
2016-2025
Second Affiliated Hospital of Xi'an Jiaotong University
2017
Eunice Kennedy Shriver National Institute of Child Health and Human Development
2011-2012
National Institutes of Health
2009-2012
University of Virginia
2004-2007
University of Missouri
2004
University of Vermont
2002
Cdt1, a protein essential in G1 for licensing of origins DNA replication, is inhibited S-phase, both by binding to geminin and degradation proteasomes. Cdt1 also degraded after damage stop new until repair. Phosphorylation cyclin-dependent kinases promotes its SCF-Skp2 E3 ubiquitin ligase, but the Cdk2/Skp2-mediated pathway not Cdt1. Here we show that N terminus contains second signal active S-phase dependent on interaction with proliferating cell nuclear antigen (PCNA) through PCNA motif....
Genomic DNA replication is tightly controlled to ensure that occurs once per cell cycle; loss of this control leads genomic instability. Geminin, a inhibitor, plays an important role in regulation replication. To investigate the human geminin maintenance stability, we eliminated by RNA interference cancer cells. Depletion led overreplication and formation giant nuclei cells had wild-type or mutant p53. We found caused depletion activated both Chk1 Chk2, which then phosphorylated Cdc25C on...
The MCM2-7 helicase complex is loaded on DNA replication origins during the G1 phase of cell cycle to license for in S phase. How initiator primase-polymerase complex, polymerase alpha (pol alpha), brought still unclear. We show that And-1/Ctf4 (Chromosome transmission fidelity 4) interacts with Mcm10, which associates MCM2-7, and p180 subunit pol alpha. And-1 essential synthesis stability mammalian cells. In Xenopus egg extracts chromatin after concurrently alpha, required efficient...
Abstract Novel therapies are urgently needed for ovarian cancer, the deadliest gynecologic malignancy. Ovarian cancer has thus far been refractory to immunotherapies that stimulate host immune system recognize and kill cells. This may be because of a suppressive tumor microenvironment lack recruitment activation cells Our previous work showed epigenetic drugs including DNA methyltransferase inhibitors histone deacetylase 6 (DNMTis HDAC6is) individually increase signaling in We find combining...
Abstract Poly-(ADP-ribose) polymerase inhibitors (PARPi) selectively kill breast and ovarian cancers with defects in homologous recombination (HR) caused by BRCA1/2 mutations. There is also clinical evidence for the utility of PARPi without BRCA mutations, but underlying mechanism not clear. Here, we report that deubiquitylating enzyme USP15 affects cancer cell response to regulating HR. Mechanistically, recruited DNA double-strand breaks (DSBs) MDC1, which requires FHA domain MDC1...
Unlike nuclear (n)DNA, of which there is one paired copy per cell, are many copies mitochondrial (mt)DNA making PCR amplification mtDNA easier in samples limited cellularity. The aims this study were to (i) determine the mutation patterns breast cancers through a comprehensive screen mutations, and (ii) assess if mutations also detectable nipple aspirate fluid (NAF), physiologic contains shed ductal epithelial cells. Fifteen cancers, matched benign tissues NAF collected. Nine overlapping...
Abstract Eukaryotic cells normally restrict genome duplication to once per cell division. In metazoa, re-replication of DNA during a single S phase seems be prevented solely by suppressing CDT1 activity, protein required for loading the replicative MCM helicase. However, siRNA suppression geminin (a specific inhibitor CDT1) arrested proliferation only derived from cancers inducing and damage that spontaneously triggered apoptosis. None these effects were detected either in normal human...
Abstract Cyclin-dependent kinases 4 and 6 (CDK4/6) play a pivotal role in cell cycle cancer development. Targeting CDK4/6 has demonstrated promising effects against breast cancer. However, resistance to inhibitors (CDK4/6i), such as palbociclib, remains substantial challenge clinical settings. Using high-throughput combinatorial drug screening genomic sequencing, we find that the microphthalmia-associated transcription factor (MITF) is activated via O-GlcNAcylation by O-GlcNAc transferase...
Abstract Cyclin-dependent kinases 4 and 6 (CDK4/6) are crucial in regulating cell cycle progression cancer development. Targeting CDK4/6 has shown considerable promise treating various cancers, including breast cancer. Despite significant therapeutic efficacy, resistance to inhibitors (CDK4/6i), such as palbociclib, remains a substantial hurdle clinical practice. Using co-culture system, cytokine array, quantitative high-throughput combinatorial screening (qHTCS), we discovered mechanism by...
The timely assembly of prereplicative complexes at replication origins is tightly controlled to ensure that genomic DNA replicated once per cell cycle.The loss geminin, a inhibitor, causes rereplication activates G 2 /M checkpoint in human cancer cells.Fanconi anemia (FA) an autosomal recessive and X-linked disorder associated with susceptibility.Here we show the FA pathway both for activation repair processes, like recruitment RAD51.Both ATR BRCA1 are required activate pathway.The...
Abstract Purpose: Up to 80% of patients with ovarian cancer develop platinum resistance over time platinum-based chemotherapy. Increased HIF1α level is an important mechanism governing in platinum-resistant (PROC). However, the regulating stability PROC remains largely unknown. Here, we elucidate regulation and explore therapeutic approaches overcome cisplatin cancer. Experimental Design: We first used a quantitative high-throughput combinational screen (qHTCS) identify novel drugs that...
Abstract The JAK2/STAT pathway is hyperactivated in many cancers, and such hyperactivation associated with a poor clinical prognosis drug resistance. mechanism regulating JAK2 activity complex. Although translocation of between nucleus cytoplasm an important regulatory mechanism, how regulated what the physiological function this remain largely unknown. Here, we found that protease SENP1 directly interacts deSUMOylates JAK2, deSUMOylation leads to its accumulation at cytoplasm, where...
// Alex Vassilev 1 , Chrissie Y. Lee 1, 2 Boris Wenge Zhu 3 Pinar Ormanoglu 4 Scott E. Martin 4, 5 Melvin L. DePamphilis National Institute of Child Health and Human Development, Institutes Health, Bethesda, MD 20892-2753, USA Current address: NantBioscience, Culver City, CA 90232, Department Biochemistry Molecular Biology, George Washington University, DC 20037, Center Advancing Translational Sciences, Rockville, 20850, Address: Genentech, Inc., South San Francisco, 94080, Correspondence...
Homologous recombination (HR) is a major mechanism to repair DNA double-strand breaks (DSBs). Although tumor suppressor CtIP critical for DSB end resection, key initial event of HR repair, the regulating recruitment sites remains largely unknown. Here, we show that acidic nucleoplasmic DNA‐binding protein 1 (And‐1) forms complexes with as well other proteins, and essential by resection. Furthermore, And-1 recruited in manner dependent on MDC1, BRCA1 ATM, down-regulation impairs resection...
Abstract DNA rereplication leads to genomic instability and has been implicated in the pathology of a variety human cancers. Eukaryotic replication is tightly controlled ensure it occurs only once during each cell cycle. Geminin critical component this control, prevents from occurring S, G2, early M phases by preventing MCM helicases forming prereplication complexes. targeted for degradation anaphase-promoting complex (APC/C) anaphase through G1-phase, however, accumulating evidence...
In vertebrate definitive hematopoiesis, nascent hematopoietic stem/progenitor cells (HSPCs) migrate to and reside in proliferative microenvironment for transitory expansion. this process, well-established DNA damage response pathways are vital resolve the replication stress, which is deleterious genome stability cell survival. However, detailed mechanism on repair of stress-induced during progenitor expansion remains elusive. Here we report that a novel zebrafish mutantcas003 with nonsense...