Scc1/Rad21/Mcd1 is required for sister chromatid cohesion and kinetochore function in vertebrate cells.
Proteolytic cleavage of the cohesin subunit Scc1 is a consistent feature of anaphase onset, although temporal differences exist between eukaryotes in cohesin loss from chromosome arms, as distinct from centromeres. We describe the effects of genetic deletion of Scc1 in chicken DT40 cells. Scc1 loss caused premature sister chromatid separation but did not disrupt chromosome condensation. Scc1 mutants showed defective repair of spontaneous and induced DNA damage. Scc1-deficient cells frequently failed to complete metaphase chromosome alignment and showed chromosome segregation defects, suggesting aberrant kinetochore function. Notably, the chromosome passenger INCENP did not localize normally to centromeres, while the constitutive kinetochore proteins CENP-C and CENP-H behaved normally. These results suggest a role for Scc1 in mitotic regulation, along with cohesion.
Sonoda
E
E
CREST Research Project, Japan Science and Technology Corporation, Radiation Genetics, Faculty of Medicine, Kyoto University, Konoe Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
Matsusaka
T
T
Morrison
C
C
Vagnarelli
P
P
Hoshi
O
O
Ushiki
T
T
Nojima
K
K
Fukagawa
T
T
Waizenegger
I C
IC
Peters
J M
JM
Earnshaw
W C
WC
Takeda
S
S
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002645:Chickens; D002842:Chromatids / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004260:DNA Repair; D004318:Doxycycline / Q000494:pharmacology; D005434:Flow Cytometry; D005656:Fungal Proteins; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018386:Kinetochores / Q000378:metabolism*; D046911:Macromolecular Substances; D018625:Microscopy, Atomic Force; D008856:Microscopy, Fluorescence; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D010750:Phosphoproteins; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins
D000900:Anti-Bacterial Agents; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004318:Doxycycline; D005656:Fungal Proteins; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D010750:Phosphoproteins; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; C083767:INCENP protein, human; C490529:MCD1 protein, S cerevisiae