A5064983130- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Telomeres, Telomerase, and Senescence
- Acute Lymphoblastic Leukemia research
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- Nuclear Structure and Function
- Advanced biosensing and bioanalysis techniques
- Cancer therapeutics and mechanisms
- BRCA gene mutations in cancer
- Mechanisms of cancer metastasis
- RNA Interference and Gene Delivery
- Polyomavirus and related diseases
- Chromosomal and Genetic Variations
- DNA and Nucleic Acid Chemistry
- Cancer Research and Treatments
McMaster University
2012-2024
Abstract CSB, a member of the SWI2/SNF2 superfamily, is implicated in DNA double-strand break (DSB) repair. However, how it regulates this repair process poorly understood. Here we uncover that CSB interacts via its newly identified winged helix domain with RIF1, an effector 53BP1, and interaction mediates recruitment to DSBs S phase. At DSBs, remodels chromatin by evicting histones, which limits RIF1 MAD2L2 but promotes BRCA1 accumulation. The remodeling activity requires not only...
The majority of Cockayne syndrome (CS) patients carry a mutation in Syndrome group B (CSB), large nuclear protein implicated DNA repair, transcription and chromatin remodeling. However, whether CSB may play role telomere metabolism has not yet been characterized. Here, we report that physically interacts with TRF2, duplex telomeric binding essential for protection. We find localizes at small subset human telomeres it is required preventing the formation dysfunction-induced foci (TIF) CS...
CSB, a member of the SWI2/SNF2 superfamily, has been implicated in evicting histones to promote DSB pathway choice towards homologous recombination (HR) repair. However, how CSB promotes HR repair remains poorly characterized. Here we demonstrate that interacts with both MRE11/RAD50/NBS1 (MRN) and BRCA1 cell cycle regulated manner, former requiring its WHD occurring predominantly early S phase. BRCT domain this interaction is by CDK-dependent phosphorylation on S1276. The CSB-BRCA1...
ABSTRACT Elevated replication stress is evident at telomeres of about 10-15% cancer cells, which maintain their via a homologous recombination (HR)-based mechanism, referred to as alternative lengthening (ALT). How ALT cells resolve support growth remains incompletely characterized. Here, we report that CSB (also known ERCC6) promotes recruitment HR repair proteins (MRN, BRCA1, BLM and RPA32) POLD3 telomeres, process requires the ATPase activity controlled by ATM- CDK2-dependent...
CSB (Cockayne syndrome group B) and SMARCAL1 (SWI/SNF-related, matrix-associated, actin-dependent, regulator of chromatin, subfamily A-like 1) are DNA translocases that belong to the SNF2 helicase family. They both enriched at stalled replication forks. While is recruited by RPA32 forks, little known about whether also regulates CSB's association with Here, we report directly interacts RPA, least in part via a RPA32C-interacting motif within N-terminal region CSB. Modeling CSB-RPA32C...
Cockayne syndrome group B protein (CSB), a member of the SWI/SNF superfamily, resides in an elongating RNA polymerase II (RNAPII) complex and regulates transcription elongation. CSB contains C-terminal winged helix domain (WHD) that binds to ubiquitin plays important role DNA repair. However, little is known about CSB-WHD regulation. Here, we report dependent upon its WHD regulate RNAPII abundance at promoter proximal pause (PPP) sites several actively transcribed genes, key step regulation...
Abstract Cockayne syndrome group B (CSB) protein has been implicated in the repair of a variety DNA lesions that induce replication stress. However, little is known about its role at stalled forks. Here, we report CSB recruited to forks manner dependent upon T1031 phosphorylation by CDK. While dispensable for MRE11 association with wild-type cells, required further accumulation BRCA1/2-deficient cells. promotes MRE11-mediated fork degradation possesses an intrinsic ATP-dependent reversal...
Topoisomerase inhibitor camptothecin (CPT) induces fork stalling and is highly toxic to proliferating cells. However, how cells respond CPT-induced has not been fully characterized. Here, we report that Cockayne syndrome group B (CSB) protein inhibits PRIMPOL-dependent repriming in response a low dose of CPT. At high concentration CPT, CSB required promote the restart DNA replication through MUS81–RAD52–POLD3-dependent break-induced (BIR). In absence CSB, resumption synthesis at CPT can...