Loss of SLX4IP leads to common fragile site instability and compromises DNA interstrand crosslink repair in vivo.

ABSTRACT: Common fragile sites (CFSs) are chromosomal loci with inherent characteristics that make them difficult to fully replicate thus rendering them vulnerable to replication stress (RS). Under-replicated CFSs manifest as cytogenetic gaps and breaks on metaphase chromosomes. Moreover, CFSs are hotspots for tumorigenic chromosomal rearrangements. The Fanconi anemia (FA) pathway is at the core of a network of proteins that work to safeguard CFSs during replication and RS. Here, we uncover a novel role of SLX4IP in maintaining CFS stability. We show that SLX4IP localizes stressed CFSs and that its loss exacerbates genome instability, including CFS expression. Furthermore, direct SLX4IP depletion leads to impaired replication and growth deficiencies. SLX4IP and FANCP/SLX4 are epistatic, suggesting t

SUBMITTER: Ingham A 

PROVIDER: S-EPMC12221885 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature