Condensin II subunit NCAPH2 associates with shelterin protein TRF1 and is required for telomere stability. Issue 11 (26th April 2019)

• Record Type: Journal Article
• Authors: Wallace, Heather A.; Rana, Vibhuti; Nguyen, Huy Q.; Bosco, Giovanni
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 11(2019:Nov.)
• Page Start: 20755
• Page End: 20768
• Publication Date: 2019-04-26
• Subjects: condensin -- DNA damage -- replication -- shelterin -- telomeres -- TRF1; Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.28681
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Condensin II subunits are known to be expressed and localized to interphase nuclei of eukaryotic cells. Although some studies have shown that condensin II likely exerts axial compaction forces, organizes chromosome territories, and has possible transcriptional modulatory functions, the full range of condensin II interphase activities are not known. In particular, it is not known if condensin II interphase activities are generally genome‐wide or if they have additional local activities unique to specific chromosomal structures such as telomeres. Here, we find that NCAPH2 interacts with TRF1 and these two proteins co‐localize at telomeres. Depletion of NCAPH2 leads to ATR‐dependent accumulation of 53BP1 and γH2AX DNA damage foci, including damage specific to telomeres. Furthermore, depletion of NCAPH2 results in a fragile telomere phenotype and apparent sister‐telomere fusions only days after NCAPH2 depletion. Taken together these observations suggest that NCAPH2 promotes telomere stability, possibly through a direct interaction with the TRF1 shelterin component, and prevents telomere dysfunction resulting from impaired DNA replication. Because proper telomere function is essential for chromosome integrity these observations reveal a previously unappreciated function for NCAPH2 in ensuring genome and telomere stability. Abstract : The condensin II subunit NCAPH2 localizes to human telomeres and interacts with the TRF1 telomere binding protein. Depletion of NCAPH2 leads to DNA damage foci at telomeres and structural defects that lead to end‐to‐end fusions. DNA damage signaling after NCAPH2 depletion is ATR dependent, suggesting that DNA replication stress and/or replication associated damage is causing telomere structural defects.