SPRTN protease and checkpoint kinase 1 cross-activation loop safeguards DNA replication (CROSBI ID 278278)
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Podaci o odgovornosti
Halder, Swagata ; Torrecilla, Ignacio ; Burkhalter, Martin D. ; Popović, Marta ; Fielden, John ; Vaz, Bruno ; Oehler, Judith ; Pilger, Domenic ; Lessel, Davor ; Wiseman, Katherine ; Singh, Abhay Narayan ; Vendrell, Iolanda ; Fischer, Roman ; Philipp, Melanie ; Ramadan, Kristijan
engleski
SPRTN protease and checkpoint kinase 1 cross-activation loop safeguards DNA replication
The SPRTN metalloprotease is essential for DNA-protein crosslink (DPC) repair and DNA replication in vertebrate cells. Cells deficient in SPRTN protease exhibit DPC-induced replication stress and genome instability, manifesting as premature ageing and liver cancer. Here, we provide a body of evidence suggesting that SPRTN activates the ATR-CHK1 phosphorylation signalling cascade during physiological DNA replication by proteolysis-dependent eviction of CHK1 from replicative chromatin. During this process, SPRTN proteolyses the Cterminal/inhibitory part of CHK1, liberating N-terminal CHK1 kinase active fragments. Simultaneously, CHK1 full length and its N-terminal fragments phosphorylate SPRTN at the C-terminal regulatory domain, which stimulates SPRTN recruitment to chromatin to promote unperturbed DNA replication fork progression and DPC repair. Our data suggest that a SPRTN-CHK1 cross-activation loop plays a part in DNA replication and protection from DNA replication stress. Finally, our results with purified components of this pathway further support the proposed model of a SPRTN-CHK1 cross-activation loop.
SPRTN ; Chk1 ; DNA replication ; DNA-protein crosslinks
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nije evidentirano
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Podaci o izdanju
Povezanost rada
Biologija, Interdisciplinarne prirodne znanosti, Kemija