Faithful chromosome segregation in eukaryotes relies on physical cohesion between newly duplicated sister chromatids. Cohesin is a ring-shaped ATPase assembly that mediates sister chromatid cohesion through its ability to topologically entrap DNA. Cohesin, assisted by several regulatory proteins, binds to DNA prior to DNA replication and then holds two sister DNAs together when it encounters the replication machinery. Cohesion establishment further requires cohesin acetylation, which confers near eternal stability on chromatin-bound cohesin until the onset of chromosome segregation. In addition to a wealth of experimental evidence from cellular studies, recent advances in reconstitution approaches are now beginning to unravel the biochemical properties of cohesin that underlie its function in sister chromatid cohesion. This review summarizes recent insights into the mechanism of cohesion establishment.
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http://dx.doi.org/10.1016/j.ceb.2025.102464 | DOI Listing |
Curr Opin Cell Biol
January 2025
Department of Chromosome Science, National Institute of Genetics, Mishima, 411-8540, Japan; Department of Genetics, Graduate University for Advanced Studies (SOKENDAI), Mishima, 411-8540, Japan. Electronic address:
Faithful chromosome segregation in eukaryotes relies on physical cohesion between newly duplicated sister chromatids. Cohesin is a ring-shaped ATPase assembly that mediates sister chromatid cohesion through its ability to topologically entrap DNA. Cohesin, assisted by several regulatory proteins, binds to DNA prior to DNA replication and then holds two sister DNAs together when it encounters the replication machinery.
View Article and Find Full Text PDFRedox Biol
January 2025
University of Chicago, Department of Molecular Genetics and Cell Biology, 929 E. 57th Street, Chicago, IL, 60637, USA. Electronic address:
During its catalytic cycle, the homodimeric ATPase topoisomerase II alpha (TOP2A) cleaves double stranded DNA and remains covalently bound to 5' ends via tyrosine phosphodiester bonds. After passing a second, intact duplex through, TOP2A rejoins the break and releases from the DNA. Thereby, TOP2A can relieve strain accumulated during transcription, replication and chromatin remodeling and disentangle sister chromatids for mitosis.
View Article and Find Full Text PDFIndian J Occup Environ Med
December 2024
Viral Research and Diagnostic Laboratory (VRDL), Government Medical College, Patiala, Punjab, India.
Pesticides induce oxidative DNA damage and genotoxic effects such as DNA single-strand breaks (SSBs), double-strand breaks (DSBs), DNA adducts, chromosomal aberrations, and enhanced sister chromatid exchanges. Such DNA damage can be repaired by DNA repair mechanisms. In humans, single nucleotide polymorphisms (SNPs) are present in DNA repair genes involved in base excision repair (BER) (, and nucleotide excision repair (NER) (, , , and ), and double-strand break repair (DSBR) ( and ).
View Article and Find Full Text PDFEMBO Rep
January 2025
Department of Biochemistry, University of Toronto, 1 King's College Circle, Toronto, ON, M5S 1A8, Canada.
Homologous recombination is a largely error-free DNA repair mechanism conserved across all domains of life and is essential for the maintenance of genome integrity. Not only are the mutations in homologous recombination repair genes probable cancer drivers, some also cause genetic disorders. In particular, mutations in the Bloom (BLM) helicase cause Bloom Syndrome, a rare autosomal recessive disorder characterized by increased sister chromatid exchanges and predisposition to a variety of cancers.
View Article and Find Full Text PDFDNA double strand breaks (DSBs) are widely considered the most cytotoxic DNA lesions occurring in cells because they physically disrupt the connectivity of the DNA double helix. Homologous recombination (HR) is a high-fidelity DSB repair pathway that copies the sequence spanning the DNA break from a homologous template, most commonly the sister chromatid. How both DNA ends, and the sister chromatid are held in close proximity during HR is unknown.
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