Replication-stress response shapes Leishmania genome plasticity through non-equivalent RAD9 and HUS1 functions.

Partial depletion of HUS1 or RAD9 in Leishmania major triggers opposing replication-stress responses, yielding distinct genome remodelling patterns during methotrexate selection.

• Why it matters: Genome plasticity supports adaptation in Leishmania, but it is unclear how conserved checkpoint surveillance subunits shape gene copy-number variation and mosaic aneuploidy.
• What they did: Cells with partial HUS1 or RAD9 depletion were subjected to methotrexate selection, and outcomes were assessed for DHFR-TS amplification patterns, genome-wide rearrangements, and HUS1/RAD9 occupancy near repetitive DNA.
• The result: HUS1 deficiency restricted DHFR-TS amplification and favored linear amplicons with fewer but larger rearrangements, while RAD9 deficiency supported extensive circular amplification with largely wild-type rearrangement burden and broader aneuploidy shifts.

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