BLM is Required for Faithful Chromosome Segregation and Its Localization Defines a Class of Ultrafine Anaphase Bridges

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2007 Jun 30

PMID 17599064

Citations 248

Authors

Kok-Lung Chan

Phillip S North

Ian D Hickson

Affiliations

Soon will be listed here.

Abstract

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 IIIalpha 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.

Citing Articles

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SRBD1 facilitates chromosome segregation by promoting topoisomerase IIα localization to mitotic chromosomes.

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The BLM-TOP3A-RMI1-RMI2 proximity map reveals that RAD54L2 suppresses sister chromatid exchanges.

Ho J, Cheng E, Wong C, St-Germain J, Dunham W, Raught B EMBO Rep. 2025; 26(5):1290-1314.

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The interplay of the translocase activity and protein recruitment function of PICH in ultrafine anaphase bridge resolution and genomic stability.

Kong N, Chen K, Chanboonyasitt P, Jiang H, Wong K, Ma H Nucleic Acids Res. 2024; 53(3).

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PMID: 39652599 PMC: 11670948. DOI: 10.1371/journal.pgen.1011515.

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