PDIP38 is a novel mitotic spindle-associated protein that affects spindle organization and chromosome segregation.
In order to maintain genomic integrity during mitosis, cells assemble the mitotic spindle to separate sister chromosomes to the two daughter cells. A variety of motor- and non motor-proteins are involved in the organization and regulation of this complex apparatus. DNA polymerase delta-interacting protein 38 (PDIP38) is a highly conserved protein and has so far been shown to be a cytoplasmic and nuclear protein. Cell cycle dependent nuclear localization and the interaction with DNA polymerase delta and proliferating cell nuclear antigen (PCNA) indicate a role for PDIP38 in DNA modification and/or proliferation. Here, we show for the first time that PDIP38 localizes to the mitotic spindle throughout mitosis. Using anti-PDIP38 antibody injections and siRNA silencing, we demonstrate that PDIP38 loss-of-function causes problems with spindle organization, aberrant chromosome segregation, and multinucleated cells. Taken together, the data indicate different roles for PDIP38 in safeguarding a proper cell division at various stages of the cell cycle, including DNA synthesis and repair, organization of the mitotic spindle and chromosome segregation.
Department of Cell and Molecular Biology, Medical Nobel Institute, Karolinska Institutet, Stockholm, Sweden. esther.klaile@ki.se
Esther
E
Klaile
Alexander
A
Kukalev
Björn
B
Obrink
Mario M
MM
Müller
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D020090:Chromosome Segregation; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D051381:Rats; D008941:Spindle Apparatus / Q000378:metabolism* / Q000648:ultrastructure
D018797:Cell Cycle Proteins; D007074:Immunoglobulin G; D009687:Nuclear Proteins; C533897:PDIP38 protein, rat; D004247:DNA