Vertebrate CTF18 and DDX11 essential function in cohesion is bypassed by preventing WAPL-mediated cohesin release
Open Access
- 9 September 2021
- journal article
- research article
- Published by Cold Spring Harbor Laboratory in Genes & Development
- Vol. 35 (19-20), 1368-1382
- https://doi.org/10.1101/gad.348581.121
Abstract
The alternative PCNA loader containing CTF18-DCC1-CTF8 facilitates sister chromatid cohesion (SCC) by poorly defined mechanisms. Here we found that in DT40 cells, CTF18 acts complementarily with the Warsaw breakage syndrome DDX11 helicase in mediating SCC and proliferation. We uncover that the lethality and cohesion defects of ctf18 ddx11 mutants are associated with reduced levels of chromatin-bound cohesin and rescued by depletion of WAPL, a cohesin-removal factor. On the contrary, high levels of ESCO1/2 acetyltransferases that acetylate cohesin to establish SCC do not rescue ctf18 ddx11 phenotypes. Notably, the tight proximity of sister centromeres and increased anaphase bridges characteristic of WAPL-depleted cells are abrogated by loss of both CTF18 and DDX11. The results reveal that vertebrate CTF18 and DDX11 collaborate to provide sufficient amounts of chromatin-loaded cohesin available for SCC generation in the presence of WAPL-mediated cohesin-unloading activity. This process modulates chromosome structure and is essential for cellular proliferation in vertebrates.Keywords
Funding Information
- Italian Association for Cancer Research (IG 18976, IG 23710)
- European Research Council (682190)
- JSPS KAKENHI (17K17986)
- Structured International Post Doc Program
- FP7 Marie Curie Actions-People
- AIRC (Mario e Valeria Rindi, Rif.22403)
- EMBO (ALTF 561-2014)
- AIRC/Marie Curie Actions-COFUND (iCARE)
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