A short nucleophosmin isoform couples nucleolar remodeling to DNA damage repair during meiosis

Nucleoli are nuclear compartments wherein ribosome biogenesis occurs. Observations spanning over a century have demonstrated that meiotic male germ cell nucleoli have unusual morphology and a close association with a large DNA damage repair foci formed around the sex chromosomes termed the XY-body. A mechanistic understanding of this relationship and its impact on ribosome biogenesis has remained elusive. High-resolution microscopy revealed XY-body associated nucleoli have an unusual two-part morphology made up of an XY-body intercalated and an XY-body adjacent part, each marked by different isoforms of the nucleolar protein nucleophosmin. Additionally, the entire structure is transcriptionally inactive and likely derived from autosomal nucleoli. Further, proper formation and maintenance of the structure rely on an interaction between NPM1 and the DNA damage marker {gamma}H2AX. These findings provide mechanistic insight into the XY-body and nucleolus association and reveal unrecognized connections between nucleolar proteins, ribosome biogenesis, and DNA damage repair during meiosis.