Evidence that the tumor-suppressor protein BRCA2 does not regulate cytokinesis in human cells.
Germline mutations in the tumor-suppressor gene BRCA2 predispose to breast and ovarian cancer. BRCA2 plays a well-established role in maintaining genome stability by regulating homologous recombination. BRCA2 has more recently been implicated in cytokinesis, the final step of cell division, but the molecular basis for this remains unknown. We have used time-lapse microscopy, recently developed cytokinesis assays and BAC recombineering (bacterial artificial chromosome recombinogenic engineering) to investigate the function and localization of BRCA2 during cell division. Our analysis suggests that BRCA2 does not regulate cytokinesis in human cells. Thus, cytokinesis defects are unlikely to contribute to chromosomal instability and tumorigenesis in BRCA2-related cancers.
Lekomtsev
Sergey
S
Cell Division and Aneuploidy Laboratory, Cancer Research UK London Research Institute, Clare Hall Laboratories, Blanche Lane, South Mimms, Hertfordshire EN6 3LD, UK.
Guizetti
Julien
J
Pozniakovsky
Andrei
A
Gerlich
Daniel W
DW
Petronczki
Mark
M
D051017:Apoptosis Regulatory Proteins; D024682:BRCA2 Protein / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D022202:Chromosomes, Artificial, Bacterial / Q000378:metabolism; D048749:Cytokinesis; D018390:Gene Targeting; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051135:Rad51 Recombinase / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D034741:RNA, Small Interfering; D051135:Rad51 Recombinase