Retinoblastoma susceptibility protein, Rb, possesses multiple BRCT-Ws, BRCA1 carboxyl-terminus-related W regions with DNA break-binding activity

Yamane, Kunio; Katayama, Eisaku; Sugasawa, Kaoru; Tsuruo, Takashi

doi:10.1038/sj.onc.1203528

Cited by 11 publications

(20 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A short p53 portion was faintly similar to those in BRCT-Ws (Figure 1a,b, in bold). Deletion analyses showed that the portion of BRCT-W1 in Rb was essential for DNA binding, and the BRCT-W4 that contained the corresponding portion also showed DNA break binding activity (Yamane et al, 2000a). The characteristic residues of the portions were aromatic residues, mainly Trp (W), but also Phe (F) and Tyr (Y).…”

Section: Resultsmentioning

confidence: 99%

“…The corresponding portion of p53 contained Tyr and Phe with four residues composed of more than two hydrophobic residues at its C-terminal side. This short stretch is another feature of W boxes of BRCTs and BRCT-Ws (Yamane et al, 2000a). We designated this portion the B53 motif.…”

Section: Resultsmentioning

confidence: 99%

“…This region bound linearized pUC19 DNA with any termini created by restriction enzymes, EcoO109I (5' protruding ends), SmaI (blunt ends), and PstI (3' protruding ends) ( Figure 4b). The independence from terminal forms, including blunt ends, was also observed in Ku DNA end binding protein (Mimori and Hardin, 1986) and in some BRCTs (Yamane and Tsuruo, 1999) and BRCTWs (Yamane et al, 2000a).…”

Section: Dna Binding Properties Of Proteins With B53mentioning

confidence: 97%

“…Taken together, we expected that p53 C-terminus would contain a common element similar to those of BRCTs. In this study, we indicate that a short motif of p53 in the Cterminus was weakly similar to a functional portion of BRCT-W1 in Rb (Yamane et al, 2000a), and was required for DNA binding and for polymerization. The multimerizing features that are well known in Rb and p53 can be consistently explained from the molecular point of view elucidated herein.…”

Section: Introductionmentioning

confidence: 92%

See 3 more Smart Citations

p53 contains a DNA break-binding motif similar to the functional part of BRCT-related region of Rb

2001

Self Cite

View full text Add to dashboard Cite

The BRCT regions are two repeating structures at BRCA1 carboxyl-terminus and are ubiquitous in some proteins involved in DNA repair and cell cycle checkpoints. It was shown that BRCTs of TopBP1, BRCA1, and BRCT-Ws of Rb bound DNA ends and breaks. We indicate here that the C-terminus of p53 tumor suppressor contains a DNA binding motif (residues 327 ± 333 in human), whose features are similar to those of the part of BRCT-W in Rb with DNA binding activity. The short motif was required for the gel retardation activity of DNA fragments, since residues 311 ± 333 showed the activity while residues 311 ± 326 showed no activity. Signi®cant numbers of total p53 and its fragments with the motif formed multimerizing complexes and associated with DNA ends and breaks. These results suggest the common presence of DNA binding motifs that can recognize DNA ends or damages in major tumor suppressors, Rb, BRCA1 and p53. The oncogenic activity of p53 C-terminus (residues 311 ± 393) required both the DNA damage recognition motif and the repair enzyme-associating domain. Oncogene (2001) 20, 2859 ± 2867.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Dna Binding Properties Of Proteins With B53mentioning

confidence: 97%

Section: Introductionmentioning

confidence: 92%

See 2 more Smart Citations

p53 contains a DNA break-binding motif similar to the functional part of BRCT-related region of Rb

2001

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, the surfaces on BRCT domains involved in binding to p53 (18,52), ␥-H2AX (62,97), and XRCC4 (21,89) have been determined. In addition some BRCT domains are known to directly bind DNA, particularly DNA ends (57,114,115). Moreover, BRCT domains have also been implicated in transcriptional activation and chromatin unfolding (40,111,118).…”

mentioning

confidence: 99%

Evidence for a Structural Relationship between BRCT Domains and the Helicase Domains of the Replication Initiators Encoded by thePolyomaviridaeandPapillomaviridaeFamilies of DNA Tumor Viruses

Kumar

Joo

Meinke

et al. 2008

J Virol

View full text Add to dashboard Cite

Studies of DNA tumor viruses have provided important insights into fundamental cellular processes and oncogenic transformation. They have revealed, for example, that upon expression of virally encoded proteins, cellular pathways involved in DNA repair and cell cycle control are disrupted. Herein, evidence is presented that BRCT-related regions are present in the helicase domains of the viral initiators encoded by the Polyomaviridae and Papillomaviridae viral families. Of interest, BRCT domains in cellular proteins recruit factors involved in diverse pathways, including DNA repair and the regulation of cell cycle progression. Therefore, the viral BRCT-related regions may compete with host BRCT domains for particular cellular ligands, a process that would help to explain the pleiotropic effects associated with infections with many DNA tumor viruses.BRCT domains were discovered following characterization of the BRCA1 (breast cancer tumor suppressor protein) C terminus (58). Subsequent sequence-based genome searches revealed that BRCT domains are present in hundreds of additional proteins (57). The BRCT domains are frequently found as tandem repeats at the C termini of proteins; however, BRCT motifs also occur as monomers that are located at many different positions relative to the N and C termini (6,46). Observations, such as those that demonstrated that the BRCT domains in BRCA1 are hot spots for oncogenic mutations (reviewed in reference 34), established the clinical importance of BRCT domains.Members of the BRCT superfamily have been identified based on certain conserved sequence features; these include clusters of hydrophobic residues and two signature motifs (6) (discussed below). Structural criteria have also been used to define BRCT domains. For example, based on the structures of the BRCT repeats in the XRCC1 protein (120) and human BRCA1 (108), it was concluded that BRCT domains consist of a four-stranded parallel ␤-sheet flanked by two ␣-helices on one side (␣1 and ␣3) and by a single ␣-helix (␣2) on the other. However, there is some variability in terms of the structural features that define BRCT domains; for instance, it is not clear whether the poorly conserved ␣2 region is present in certain BRCT members (e.g., DNA ligase III [59] and the second BRCT repeat of rat BRCA1 [52,59]). In addition, the BRCT repeats in 53BP1, a p53 interacting protein (47), have ␣-helical inserts between their ␤2 and ␤3 strands (i.e., ␣1Ј) that are not found in other BRCT domains (52). Moreover, while the canonical BRCT domain contains a four-stranded parallel ␤-sheet, the REV1 protein is predicted to have only three parallel ␤-strands at the core of its BRCT domain (57).The primary function of BRCT domains is to serve as scaffolds that recruit cellular proteins, many of which are involved in cell cycle checkpoints and DNA recombination, repair, and replication (reviewed in references 5, 6, and 46). Owing to the determination of several costructures, the residues in BRCT domains that serve as binding sites for individual pro...

show abstract

The BRCT Regions of Tumor Suppressor BRCA1 and of XRCC1 Show DNA End Binding Activity with a Multimerizing Feature

Yamane

Katayama

Tsuruo

2000

Biochemical and Biophysical Research Communications

Self Cite

View full text Add to dashboard Cite

Retinoblastoma susceptibility protein, Rb, possesses multiple BRCT-Ws, BRCA1 carboxyl-terminus-related W regions with DNA break-binding activity

Cited by 11 publications

References 38 publications

p53 contains a DNA break-binding motif similar to the functional part of BRCT-related region of Rb

p53 contains a DNA break-binding motif similar to the functional part of BRCT-related region of Rb

Evidence for a Structural Relationship between BRCT Domains and the Helicase Domains of the Replication Initiators Encoded by thePolyomaviridaeandPapillomaviridaeFamilies of DNA Tumor Viruses

The BRCT Regions of Tumor Suppressor BRCA1 and of XRCC1 Show DNA End Binding Activity with a Multimerizing Feature

Contact Info

Product

Resources

About