Abstract:
:Approximately 30% of human tumors examined for mutations in polymerase beta (pol beta) appear to express pol beta variant proteins (D. Starcevic, S. Dalal, and J. B. Sweasy, Cell Cycle 3:998-1001, 2004). Many of these variants result from a single amino acid substitution. We have previously shown that the K289M and I260M colon and prostate cancer variants, respectively, induce cellular transformation most likely due to sequence-specific mutator activity (S. Dalal et al., Biochemistry 44:15664-15673, 2005; T. Lang et al., Proc. Natl. Acad. Sci. USA 101:6074-6079, 2004; J. B. Sweasy et al., Proc. Natl. Acad. Sci. USA 102:14350-14355, 2005). In the work described here, we show that the E295K gastric carcinoma pol beta variant acts in a dominant-negative manner by interfering with base excision repair. This leads to an increase in sister chromatid exchanges. Expression of the E295K variant also induces cellular transformation. Our data suggest that unfilled gaps are channeled into a homology-directed repair pathway that could lead to genomic instability. The results indicate that base excision repair is critical for maintaining genome stability and could therefore be a tumor suppressor mechanism.
journal_name
Mol Cell Bioljournal_title
Molecular and cellular biologyauthors
Lang T,Dalal S,Chikova A,DiMaio D,Sweasy JBdoi
10.1128/MCB.01883-06subject
Has Abstractpub_date
2007-08-01 00:00:00pages
5587-96issue
15eissn
0270-7306issn
1098-5549pii
MCB.01883-06journal_volume
27pub_type
杂志文章abstract::The E2F1, -2, and -3 transcription factors are key downstream targets of the retinoblastoma protein (pRB) tumor suppressor that drive expression of proliferation-associated genes. Here we use mutant mouse strains to investigate E2F3's role in vivo. We show that E2F3 is essential for embryonic viability in the pure 129...
journal_title:Molecular and cellular biology
pub_type: 杂志文章
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2009-05-01 00:00:00
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更新日期:1995-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:1987-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:1987-06-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2006-08-01 00:00:00
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pub_type: 杂志文章
doi:10.1128/mcb.14.7.4565
更新日期:1994-07-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2017-08-11 00:00:00
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pub_type: 杂志文章
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更新日期:2003-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/MCB.21.20.6859-6869.2001
更新日期:2001-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.10.7.3607
更新日期:1990-07-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:1988-01-01 00:00:00
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pub_type: 杂志文章
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更新日期:1996-11-01 00:00:00
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journal_title:Molecular and cellular biology
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1994-03-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1993-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:2001-03-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1988-09-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
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更新日期:1993-12-01 00:00:00
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pub_type: 杂志文章,收录出版
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更新日期:2003-06-01 00:00:00
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journal_title:Molecular and cellular biology
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更新日期:2008-10-01 00:00:00
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journal_title:Molecular and cellular biology
pub_type: 杂志文章
doi:10.1128/mcb.11.10.5005
更新日期:1991-10-01 00:00:00
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pub_type: 杂志文章
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更新日期:2015-09-01 00:00:00