Chromosomal breakage syndromes and the BRCA1 genome surveillance complex

Futaki, Makoto; Liu, Johnson M.

doi:10.1016/s1471-4914(01)02178-5

Cited by 56 publications

(42 citation statements)

References 58 publications

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“…Among those, the N-terminal region contains a fork-head associated (FHA) domain and two breast cancer carboxy-terminal (BRCT) domains. Rs1805794 is a missense polymorphism (Glu185Gln) located in the BRCT domain of NBS1 (Kobayashi, 2004), and such a domain facilitates NBS1 to interact with breast cancer type 1 susceptibility protein (BRCA1) and form a BRCA1-associated genome surveillance complex (BASC) which is responsible for recognition and repair of aberrant DNA (Wang et al, 2000;Futaki and Liu, 2001). Thus, the Glu185Gln may interfere with protein-protein interaction and affect DNA repair capacity (Tauchi, 2000).…”

Section: 851 Variants Of Nbs1 Predict Clinical Outcome Of Chemotheramentioning

confidence: 99%

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

Hu²,

Huang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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Section: 851 Variants Of Nbs1 Predict Clinical Outcome Of Chemotheramentioning

confidence: 99%

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

Hu²,

Huang³

et al. 2012

Asian Pacific Journal of Cancer Prevention

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“…As hMSH2 and hMSH6 are thought to be major components of the BRCA1 genome surveillance repair complex (BASC) (29,30) along with other DNA repair response proteins, it was possible that BASC was trapped to the BRCT domain along with the hGCN5/TRRAP complex. Although a TFTC-like complex has been purified previously from HeLa cell nuclear extracts and shown to serve as a ligand-dependent co-activator complex for ER␣ in vitro (21), ER␣ was undetectable in the BRCT interactants by our purification procedure (Fig.…”

Section: Biochemical Purification Of Hgcn5 and Trrap As Brca1mentioning

confidence: 99%

An hGCN5/TRRAP Histone Acetyltransferase Complex Co-activates BRCA1 Transactivation Function through Histone Modification

Oishi

Kitagawa²,

Wada³

et al. 2006

Journal of Biological Chemistry

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It is well established that genetic mutations that impair BRCA1 function predispose women to early onset of breast and ovarian cancer. However, the co-regulatory factors that support normal BRCA1 functions remain to be identified. Using a biochemical approach to search for such co-regulatory factors, we identified hGCN5, TRRAP, and hMSH2/6 as BRCA1-interacting proteins. Germ line mutations in BRCA1 are known to predispose women to the early onset of breast and ovarian cancer (1, 2). The 1863-amino acid BRCA1 protein is unique in that it harbors an N-terminal RING domain and two tandem copies of BRCT 2 at its C-terminal end (8). The major function of BRCA1 is thought to be as a tumor suppressor via DNA repair and transcriptional control (9) presumably involving chromatin remodeling and histone modification (10). The transcription factor function of BRCA1, as a co-regulator of other classes of sequence-specific regulators, is dependent on the BRCT autonomous transactivation domain (11,12). The physiological significance of the BRCT domain is further supported by the finding that a number of BRCA1 mutations found in breast cancer patients involve the BRCT domain with resultant loss of transactivation function (3, 13). However, despite the pivotal role of BRCT function in BRCA1-mediated tumor suppression, little is known about the co-regulators and co-regulator complexes that support BRCT function (14).Recent progress in cell biology has revealed that chromatin remodeling and modification are indispensable for events involving chromosomal DNA. A large number of chromosomal DNA-interacting factors and complexes have been identified, and most of them appear to exhibit specific enzyme activities and chromatin remodeling functions (10, 15). For gene regulation by sequence-specific regulators and co-regulators, chromatin remodeling and modification are thought to be tightly coupled such that histone acetylation appears to often initiate gene regulation and is followed by further histone modification, including methylation and phosphorylation (10,16,17). However, the molecular mechanisms by which these processes of histone modification are controlled remain largely unknown with many histone modification complexes still to be identified. Although it is known that several histone acetyltransferases (HATs) and HAT-containing complexes co-regulate sequence-specific regulators (5, 18 -21), it is unclear whether each sequence-specific regulator requires a cognate HAT complex (or complexes) or can share common HAT complexes with other sequencespecific regulator classes.It was reported recently that the transactivation function of BRCA1 was squelched by the transactivation of ER␣ (4, 22), considered to be a critical regulator of estrogen-dependent breast cancer. ER␣ is a member of the nuclear receptor gene superfamily, acting as a hormone-dependent transcription factor, and is known to require a number of chromatin remodeling and histone modification complexes. As two HAT co-acti-* This work was supported in part by a grant-in-ai...

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“…Individuals with inherited recessive clinical syndromes, such as Nijmegen breakage syndrome (NBS), Bloom syndrome, Fanconi anemia, and ataxia telangiectasia, which are characterized by spontaneous chromosomal instability, immunodeficiency, and a predisposition to cancer, carry a mutation in one of the genes in the DNA damage signaling pathway (17,18). The gene for NBS is situated on chromosome 8q21 (19).…”

Section: Introductionmentioning

confidence: 99%

“…The product of the NBS1 gene (nibrin, also referred to as p95) is a component of the hMRE11/hRAD50/NBS1 nuclease complex (20). This complex is part of the BRCA1-associated genome surveillance complex, which is responsible for DNA damage repair (18). A 5-bp deletion in exon 6 of NBS1 (657del5) is present in the majority of NBS patients from eastern Europe (21).…”

Section: Introductionmentioning

confidence: 99%

NBS1 Is a Prostate Cancer Susceptibility Gene

et al. 2004

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To evaluate whether an inactivating mutation in the gene for the Nijmegen breakage syndrome (NBS1) plays a role in the etiology of prostate cancer, we compared the prevalence of the 657del5 NBS1 founder allele in 56 patients with familial prostate cancer, 305 patients with nonfamilial prostate cancer, and 1500 control subjects from Poland. Loss of heterozygosity analysis also was performed on DNA samples isolated from 17 microdissected prostate cancers, including 8 from carriers of the 657del5 mutation. The NBS1 founder mutation was present in 5 of 56 (9%) patients with familial prostate cancer (odds ratio, 16; P < 0.0001), 7 of 305 (2.2%) patients with nonfamilial prostate cancer (odds ratio, 3.9; P ‫؍‬ 0.01), and 9 of 1500 control subjects (0.6%). The wild-type NBS1 allele was lost in seven of eight prostate tumors from carriers of the 657del5 allele, but loss of heterozygosity was seen in only one of nine tumors from noncarriers (P ‫؍‬ 0.003). These findings suggest that heterozygous carriers of the NBS1 founder mutation exhibit increased susceptibility to prostate cancer and that the cancers that develop in the prostates of carriers are functionally homozygous for the mutation.

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Chromosomal breakage syndromes and the BRCA1 genome surveillance complex

Cited by 56 publications

References 58 publications

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

Genetic Variants of NBS1 Predict Clinical Outcome of Platinum-based Chemotherapy in Advanced Non-small Cell Lung Cancer in Chinese

An hGCN5/TRRAP Histone Acetyltransferase Complex Co-activates BRCA1 Transactivation Function through Histone Modification

NBS1 Is a Prostate Cancer Susceptibility Gene

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