BLM is required for faithful chromosome segregation and its localization defines a class of ultrafine anaphase bridges

被引:337
作者
Chan, Kok-Lung [1 ]
North, Phillip S. [1 ]
Hickson, Ian D. [1 ]
机构
[1] Univ Oxford, Canc Res UK Oxford Canc Ctr, Weatherall Inst Mol Med, John Radcliffe Hosp,Canc Res UK Labs, Oxford OX3 9DS, England
关键词
anaphase bridges; Bloom's syndrome; centromeres; chromosome segregation; PICH helicase; TOPOISOMERASE-III-ALPHA; DAMAGED REPLICATION FORKS; BLOOMS-SYNDROME HELICASE; SYNDROME GENE-PRODUCT; S-PHASE ARREST; SYNDROME PROTEIN; HOMOLOGOUS RECOMBINATION; RECQ HELICASES; SCHIZOSACCHAROMYCES-POMBE; CANCER-CELLS;
D O I
10.1038/sj.emboj.7601777
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mutations in BLM cause Bloom's syndrome, a disorder associated with cancer predisposition and chromosomal instability. We investigated whether BLM plays a role in ensuring the faithful chromosome segregation in human cells. We show that BLM-defective cells display a higher frequency of anaphase bridges and lagging chromatin than do isogenic corrected derivatives that eptopically express the BLM protein. In normal cells undergoing mitosis, BLM protein localizes to anaphase bridges, where it colocalizes with its cellular partners, topoisomerase IIIa and hRMI1 (BLAP75). Using BLM staining as a marker, we have identified a class of ultrafine DNA bridges in anaphase that are surprisingly prevalent in the anaphase population of normal human cells. These so-called BLM-DNA bridges, which also stain for the PICH protein, frequently link centromeric loci, and are present at an elevated frequency in cells lacking BLM. On the basis of these results, we propose that sister-chromatid disjunction is often incomplete in human cells even after the onset of anaphase. We present a model for the action of BLM in ensuring complete sister chromatid decatenation in anaphase.
引用
收藏
页码:3397 / 3409
页数:13
相关论文
共 52 条
[1]   PICH, a centromere-associated SNF2 family ATPase, is regulated by Plk1 and required for the spindle checkpoint [J].
Baumann, Christoph ;
Koerner, Roman ;
Hofmann, Kay ;
Nigg, Erich A. .
CELL, 2007, 128 (01) :101-114
[2]   Functional link between BLM defective in Bloom's syndrome and the ataxia-telangiectasia-mutated protein, ATM [J].
Beamish, H ;
Kedar, P ;
Kaneko, H ;
Chen, P ;
Fukao, T ;
Peng, C ;
Beresten, S ;
Gueven, N ;
Purdie, D ;
Lees-Miller, S ;
Ellis, N ;
Kondo, N ;
Lavin, MF .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (34) :30515-30523
[3]   Unfolding individual nucleosomes by stretching single chromatin fibers with optical tweezers [J].
Bennink, ML ;
Leuba, SH ;
Leno, GH ;
Zlatanova, J ;
de Grooth, BG ;
Greve, J .
NATURE STRUCTURAL BIOLOGY, 2001, 8 (07) :606-610
[4]   Regulation and localization of the Bloom syndrome protein in response to DNA damage [J].
Bischof, O ;
Kim, SH ;
Irving, J ;
Beresten, S ;
Ellis, NA ;
Campisi, J .
JOURNAL OF CELL BIOLOGY, 2001, 153 (02) :367-380
[5]   Ubc9-and mms21-mediated sumoylation counteracts recombinogenic events at damaged replication forks [J].
Branzei, Dana ;
Sollier, Julie ;
Liberi, Giordano ;
Zhao, Xiaolan ;
Maeda, Daisuke ;
Seki, Masayuki ;
Enomoto, Takemi ;
Ohta, Kunihiro ;
Foiani, Marco .
CELL, 2006, 127 (03) :509-522
[6]   MANIFOLD INCREASE IN SISTER CHROMATID EXCHANGES IN BLOOMS SYNDROME LYMPHOCYTES [J].
CHAGANTI, RS ;
SCHONBERG, S ;
GERMAN, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1974, 71 (11) :4508-4512
[7]   RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex [J].
Chang, M ;
Bellaoui, M ;
Zhang, CY ;
Desai, R ;
Morozov, P ;
Delgado-Cruzata, L ;
Rothstein, R ;
Freyer, GA ;
Boone, C ;
Brown, GW .
EMBO JOURNAL, 2005, 24 (11) :2024-2033
[8]   Architecture of the human Ndc80-Hec1 complex, a critical constituent of the outer kinetochore [J].
Ciferri, C ;
De Luca, J ;
Monzani, S ;
Ferrari, KJ ;
Ristic, D ;
Wyman, C ;
Stark, H ;
Kilmartin, J ;
Salmon, ED ;
Musacchio, A .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (32) :29088-29095
[9]   RecQ helicases: lessons from model organisms [J].
Cobb, Jennifer A. ;
Bjergbaek, Lotte .
NUCLEIC ACIDS RESEARCH, 2006, 34 (15) :4106-4114
[10]   Phosphorylation of the Bloom's syndrome helicase and its role in recovery from S-phase arrest [J].
Davies, SL ;
North, PS ;
Dart, A ;
Lakin, ND ;
Hickson, ID .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (03) :1279-1291