Summarized by Daily Strand AI from peer-reviewed source
Every time a cell divides, it must first make an exact copy of its DNA and then carefully hold the two copies — called sister chromatids — together until the moment they're pulled apart into new cells. Scientists have long known that a protein called cohesin acts like molecular glue to keep these chromosomal twins paired, but exactly how they align at the finest scale has remained unclear. Now, researchers have developed a new tool called CAD-C that reveals this pairing with unprecedented detail, showing that sister chromatids don't just loosely associate — they line up in near-perfect register, with the same individual nucleosomes (the tiny protein spools that DNA wraps around) facing each other across the two copies.
CAD-C works by using a naturally occurring enzyme called Caspase-Activated DNase, or CAD, to cut chromatin — the combined package of DNA and its associated proteins — into the smallest meaningful units: individual nucleosomes. This fine-grained chopping dramatically improves a key step called proximity ligation, where nearby DNA fragments are chemically joined together to reveal which parts of the genome are physically close in 3D space. The resulting long, linked DNA molecules are then read using Nanopore sequencing, a technology that can decode very long stretches of DNA in one pass. The combination lets researchers map not just pairs of interacting DNA regions, but complex multi-way interactions, and — crucially — tell apart the two sister copies of each chromosome. Using this approach, the team confirmed that centromeres, the specialized chromosomal regions that serve as attachment points during cell division, are closely paired between sisters, and that cohesin keeps the entire chromosome aligned with striking molecular precision.
Understanding how sister chromatids are held together matters deeply for human health. Errors in chromosome segregation — the process of pulling sister chromatids apart during cell division — are a leading cause of miscarriages, birth defects like Down syndrome, and are a hallmark of cancer cells. The discovery that cohesin enforces nucleosome-level alignment suggests the cohesion machinery is far more exquisitely organized than previously appreciated, which could reshape how scientists think about what goes wrong when chromosomes missegregate. Beyond biology, CAD-C itself is a significant methodological advance: by solving three longstanding limitations of chromosome-conformation capture techniques — low resolution, inability to detect multiway contacts, and difficulty distinguishing sister chromatids — it hands researchers a powerful new instrument for studying genome architecture. It's worth noting that the study's findings are based on specific cell systems, and broader validation across different cell types and organisms has yet to be described, so the full generality of these results remains to be established.
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