TY - JOUR
T1 - Master mitotic kinases regulate viral genome delivery during papillomavirus cell entry
AU - Rizzato, Matteo
AU - Mao, Fuxiang
AU - Chardon, Florian
AU - Lai, Kun Yi
AU - Villalonga-Planells, Ruth
AU - Drexler, Hannes C.A.
AU - Pesenti, Marion E.
AU - Fiskin, Mert
AU - Roos, Nora
AU - King, Kelly M.
AU - Li, Shuaizhi
AU - Gamez, Eduardo R.
AU - Greune, Lilo
AU - Dersch, Petra
AU - Simon, Claudia
AU - Masson, Murielle
AU - Van Doorslaer, Koenraad
AU - Campos, Samuel K.
AU - Schelhaas, Mario
N1 - Publisher Copyright:
© 2023, The Author(s).
PY - 2023/12
Y1 - 2023/12
N2 - Mitosis induces cellular rearrangements like spindle formation, Golgi fragmentation, and nuclear envelope breakdown. Similar to certain retroviruses, nuclear delivery during entry of human papillomavirus (HPV) genomes is facilitated by mitosis, during which minor capsid protein L2 tethers viral DNA to mitotic chromosomes. However, the mechanism of viral genome delivery and tethering to condensed chromosomes is barely understood. It is unclear, which cellular proteins facilitate this process or how this process is regulated. This work identifies crucial phosphorylations on HPV minor capsid protein L2 occurring at mitosis onset. L2’s chromosome binding region (CBR) is sequentially phosphorylated by the master mitotic kinases CDK1 and PLK1. L2 phosphorylation, thus, regulates timely delivery of HPV vDNA to mitotic chromatin during mitosis. In summary, our work demonstrates a crucial role of mitotic kinases for nuclear delivery of viral DNA and provides important insights into the molecular mechanism of pathogen import into the nucleus during mitosis.
AB - Mitosis induces cellular rearrangements like spindle formation, Golgi fragmentation, and nuclear envelope breakdown. Similar to certain retroviruses, nuclear delivery during entry of human papillomavirus (HPV) genomes is facilitated by mitosis, during which minor capsid protein L2 tethers viral DNA to mitotic chromosomes. However, the mechanism of viral genome delivery and tethering to condensed chromosomes is barely understood. It is unclear, which cellular proteins facilitate this process or how this process is regulated. This work identifies crucial phosphorylations on HPV minor capsid protein L2 occurring at mitosis onset. L2’s chromosome binding region (CBR) is sequentially phosphorylated by the master mitotic kinases CDK1 and PLK1. L2 phosphorylation, thus, regulates timely delivery of HPV vDNA to mitotic chromatin during mitosis. In summary, our work demonstrates a crucial role of mitotic kinases for nuclear delivery of viral DNA and provides important insights into the molecular mechanism of pathogen import into the nucleus during mitosis.
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U2 - 10.1038/s41467-023-35874-w
DO - 10.1038/s41467-023-35874-w
M3 - Article
C2 - 36683055
AN - SCOPUS:85146550989
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 355
ER -