Publication: A nuclear function for the tumor suppressor BRCAI
Authors
Monteiro A.N.A. ; Birge, R.B.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
The breast and ovarian cancer susceptibility
gene BRCAl has been recently cloned and revealed an
open reading frame of 1863 amino acids, but a lack of
significant homology to any known protein in the
database has led to few clues about its functions. One of
the first steps to investigate the function of BRCAl was
to define its subcellular localization. Several reports
have led to contradictory findings that include: nuclear
localization in normal cells and cytoplasmic in breast
and ovarian cancer cells; nuclear in both normal and
cancer cells; cytoplasmic and secreted to the extracellular
space; present in tube-like invaginations of the
nucleus; and colocalizing with the centrosome. As is
apparent, the subcellular localization has been the most
controversial aspect of BRCAl biology and is a key
point to uncover its functions. In this paper we review
the published data on subcellular localization of BRCAl
with special emphasis on the antibodies and techniques
used. We conclude that there is now overwhelming
evidence to support a nuclear localization for BRCAl,
both in normal and cancer cells. In addition, several
BRCAl-interacting proteins have been isolated and they
are preferentially located in the nucleus. Evidence
supporting a physiological function for BRCAl during
DNA repair and transcriptional activation is also
discussed.
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