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

KL Chan, PS North, ID Hickson - The EMBO journal, 2007 - embopress.org
KL Chan, PS North, ID Hickson
The EMBO journal, 2007embopress.org
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 …
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 IIIα 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.
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