PMID- 16563186
OWN - NLM
STAT- MEDLINE
DCOM- 20060731
LR  - 20181113
IS  - 1474-760X (Electronic)
IS  - 1465-6906 (Print)
IS  - 1474-7596 (Linking)
VI  - 7
IP  - 3
DP  - 2006
TI  - Phylogenetic and structural analysis of centromeric DNA and kinetochore proteins.
PG  - R23
AB  - BACKGROUND: Kinetochores are large multi-protein structures that assemble on 
      centromeric DNA (CEN DNA) and mediate the binding of chromosomes to microtubules. 
      Comprising 125 base-pairs of CEN DNA and 70 or more protein components, 
      Saccharomyces cerevisiae kinetochores are among the best understood. In contrast, 
      most fungal, plant and animal cells assemble kinetochores on CENs that are longer 
      and more complex, raising the question of whether kinetochore architecture has 
      been conserved through evolution, despite considerable divergence in CEN 
      sequence. RESULTS: Using computational approaches, ranging from sequence 
      similarity searches to hidden Markov model-based modeling, we show that organisms 
      with CENs resembling those in S. cerevisiae (point CENs) are very closely related 
      and that all contain a set of 11 kinetochore proteins not found in organisms with 
      complex CENs. Conversely, organisms with complex CENs (regional CENs) contain 
      proteins seemingly absent from point-CEN organisms. However, at least three 
      quarters of known kinetochore proteins are present in all fungi regardless of CEN 
      organization. At least six of these proteins have previously unidentified human 
      orthologs. When fungi and metazoa are compared, almost all have kinetochores 
      constructed around Spc105 and three conserved multi-protein linker complexes 
      (MIND, COMA, and the NDC80 complex). CONCLUSION: Our data suggest that critical 
      structural features of kinetochores have been well conserved from yeast to man. 
      Surprisingly, phylogenetic analysis reveals that human kinetochore proteins are 
      as similar in sequence to their yeast counterparts as to presumptive Drosophila 
      melanogaster or Caenorhabditis elegans orthologs. This finding is consistent with 
      evidence that kinetochore proteins have evolved very rapidly relative to 
      components of other complex cellular structures.
FAU - Meraldi, Patrick
AU  - Meraldi P
AD  - Department of Biology, Massachusetts Institute of Technology, Massachusetts Ave, 
      Cambridge, MA 02139, USA.
FAU - McAinsh, Andrew D
AU  - McAinsh AD
FAU - Rheinbay, Esther
AU  - Rheinbay E
FAU - Sorger, Peter K
AU  - Sorger PK
LA  - eng
GR  - R01 CA084179/CA/NCI NIH HHS/United States
GR  - R01 GM051464/GM/NIGMS NIH HHS/United States
GR  - CA84179/CA/NCI NIH HHS/United States
GR  - GM51464/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060322
PL  - England
TA  - Genome Biol
JT  - Genome biology
JID - 100960660
RN  - 0 (DNA, Fungal)
RN  - 0 (Saccharomyces cerevisiae Proteins)
SB  - IM
MH  - Centromere/*genetics
MH  - DNA Replication
MH  - DNA, Fungal/classification/*genetics
MH  - Kinetochores/*physiology
MH  - Phylogeny
MH  - Saccharomyces cerevisiae/genetics
MH  - Saccharomyces cerevisiae Proteins/genetics
PMC - PMC1557759
EDAT- 2006/03/28 09:00
MHDA- 2006/08/01 09:00
PMCR- 2006/03/22
CRDT- 2006/03/28 09:00
PHST- 2005/10/19 00:00 [received]
PHST- 2005/12/19 00:00 [revised]
PHST- 2006/02/24 00:00 [accepted]
PHST- 2006/03/28 09:00 [pubmed]
PHST- 2006/08/01 09:00 [medline]
PHST- 2006/03/28 09:00 [entrez]
PHST- 2006/03/22 00:00 [pmc-release]
AID - gb-2006-7-3-r23 [pii]
AID - 10.1186/gb-2006-7-3-r23 [doi]
PST - ppublish
SO  - Genome Biol. 2006;7(3):R23. doi: 10.1186/gb-2006-7-3-r23. Epub 2006 Mar 22.