PMID- 23810555
OWN - NLM
STAT- MEDLINE
DCOM- 20140131
LR  - 20240210
IS  - 2211-1247 (Electronic)
VI  - 4
IP  - 1
DP  - 2013 Jul 11
TI  - Cell-cycle kinases coordinate the resolution of recombination intermediates with 
      chromosome segregation.
PG  - 76-86
LID - S2211-1247(13)00272-6 [pii]
LID - 10.1016/j.celrep.2013.05.039 [doi]
AB  - Homologous recombination leads to the formation of DNA joint molecules (JMs) that 
      must be resolved to allow chromosome segregation, but how resolution is 
      temporally coupled with chromosome segregation is unknown. Here, we have analyzed 
      the role of the cell-cycle kinases Cdk and Cdc5 in coordinating these events 
      through their involvement in the phosphoregulation of the Mus81-Mms4 nuclease. By 
      identifying CDC5 and MMS4 mutants that uncouple Mus81-Mms4 activation from 
      cell-cycle progression, we show that JM disengagement, prior to anaphase 
      initiation, safeguards chromosome segregation. By simultaneously stimulating the 
      cleavage of cohesin and activating Mus81-Mms4 at the G2/M transition, Cdk and 
      Cdc5 coordinate the sequential elimination of all chromosomal interactions in 
      preparation for chromosome segregation. Conversely, untimely Cdc5 expression 
      increases crossover frequency due to premature activation of Mus81-Mms4. 
      Therefore, temporal restriction of JM resolution, imposed by Cdk/Cdc5, minimizes 
      the potential for loss of heterozygosity while preventing chromosome 
      missegregation and aneuploidy.
CI  - Copyright (c) 2013 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Matos, Joao
AU  - Matos J
AD  - London Research Institute, Cancer Research UK, Clare Hall Laboratories, South 
      Mimms, Herts EN6 3LD, UK.
FAU - Blanco, Miguel G
AU  - Blanco MG
FAU - West, Stephen C
AU  - West SC
LA  - eng
GR  - 11582/CRUK_/Cancer Research UK/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130627
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Chromosomal Proteins, Non-Histone)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.21 (CDC5 protein, S cerevisiae)
RN  - EC 2.7.11.22 (CDC28 Protein Kinase, S cerevisiae)
RN  - EC 3.1.- (Endonucleases)
RN  - EC 3.1.- (Flap Endonucleases)
RN  - EC 3.1.- (MUS81 protein, S cerevisiae)
RN  - EC 3.1.22.- (MMS4 protein, S cerevisiae)
SB  - IM
MH  - Amino Acid Sequence
MH  - CDC28 Protein Kinase, S cerevisiae/genetics/*metabolism
MH  - Cell Cycle Proteins/chemistry/genetics/*metabolism
MH  - Chromosomal Proteins, Non-Histone/metabolism
MH  - *Chromosome Segregation
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - Endonucleases/genetics/metabolism
MH  - Flap Endonucleases/genetics/metabolism
MH  - *Homologous Recombination
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Protein Serine-Threonine Kinases/chemistry/genetics/*metabolism
MH  - Saccharomyces cerevisiae/genetics/*metabolism
MH  - Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism
MH  - Cohesins
EDAT- 2013/07/03 06:00
MHDA- 2014/02/01 06:00
CRDT- 2013/07/02 06:00
PHST- 2013/03/04 00:00 [received]
PHST- 2013/05/08 00:00 [revised]
PHST- 2013/05/23 00:00 [accepted]
PHST- 2013/07/02 06:00 [entrez]
PHST- 2013/07/03 06:00 [pubmed]
PHST- 2014/02/01 06:00 [medline]
AID - S2211-1247(13)00272-6 [pii]
AID - 10.1016/j.celrep.2013.05.039 [doi]
PST - ppublish
SO  - Cell Rep. 2013 Jul 11;4(1):76-86. doi: 10.1016/j.celrep.2013.05.039. Epub 2013 
      Jun 27.