Chromosome-scale genome assembly and gene annotation of the hydrothermal vent annelid Alvinella pompejana yield insight into animal evolution in extreme environments.

Background: The Pompeii worm Alvinella pompejana, a terebellid annelid, has long been an exemplar of a metazoan that lives in an extreme environment, on the chimney wall of deep-sea hydrothermal vents, but this very environment has made it difficult to study. Comprehensive assessment of Alvinella pompejana genome content, and the factors that could explain its ability to thrive in seemingly hostile conditions has been lacking.

Results: We report the chromosome-level genome sequence of Alvinella pompejana and population-level sequence variants.

Mistimed origin licensing and activation stabilize common fragile sites under tight DNA-replication checkpoint activation.

Genome integrity requires replication to be completed before chromosome segregation. The DNA-replication checkpoint (DRC) contributes to this coordination by inhibiting CDK1, which delays mitotic onset. Under-replication of common fragile sites (CFSs), however, escapes surveillance, resulting in mitotic chromosome breaks.

Replication Stress Induces Global Chromosome Breakage in the Fragile X Genome.

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by mutations in the FMR1 gene and deficiency of a functional FMRP protein. FMRP is known as a translation repressor whose nuclear function is not understood. We investigated the global impact on genome stability due to FMRP loss.

Transcription-mediated organization of the replication initiation program across large genes sets common fragile sites genome-wide.

Common fragile sites (CFSs) are chromosome regions prone to breakage upon replication stress known to drive chromosome rearrangements during oncogenesis. Most CFSs nest in large expressed genes, suggesting that transcription could elicit their instability; however, the underlying mechanisms remain elusive. Genome-wide replication timing analyses here show that stress-induced delayed/under-replication is the hallmark of CFSs.