The Sir4 H‐
            BRCT
            domain interacts with phospho‐proteins to sequester and repress yeast heterochromatin

AbstractHereditary breast cancer constitutes 5–10% of all breast cancer cases. Inherited mutations in the BRCA1 and BRCA2 tumor-suppressor genes account for the majority of hereditary breast cancer cases. The BRCA1 C-terminal region (BRCT) has a functional duplicated globular domain, which helps with DNA damage repair and cell cycle checkpoint protein control. More than 100 distinct BRCA1 missense variants with structural and functional effects have been documented within the BRCT domain. Interpreting the results of mutation screening of tumor-suppressor genes that can have high-risk susceptibility mutations is increasingly important in clinical practice. This study includes a novel mutation, p.His1746 Pro (c.5237A>C), which was found in BRCA1 exon 20 of a breast cancer patient. In silico analysis suggests that this mutation could alter the stability and orientation of the BRCT domain and the differential binding of the BACH1 substrate.

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PTIP, a novel BRCT domain-containing protein interacts with Pax2 and is associated with active chromatin

Nucleic Acids Research ◽

10.1093/nar/28.14.2741 ◽

2000 ◽

Vol 28 (14) ◽

pp. 2741-2751 ◽

Cited By ~ 44

Author(s):

M. S. Lechner

Keyword(s):

Brct Domain ◽

Active Chromatin

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Efficient Single-Strand Break Repair Requires Binding to Both Poly(ADP-Ribose) and DNA by the Central BRCT Domain of XRCC1

Cell Reports ◽

10.1016/j.celrep.2018.12.082 ◽

2019 ◽

Vol 26 (3) ◽

pp. 573-581.e5 ◽

Cited By ~ 18

Author(s):

Luis M. Polo ◽

Yingqi Xu ◽

Peter Hornyak ◽

Fernando Garces ◽

Zhihong Zeng ◽

...

Keyword(s):

Strand Break ◽

Single Strand ◽

Brct Domain ◽

Single Strand Break ◽

Single Strand Break Repair ◽

Break Repair

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BRCT Domain-Containing Protein PTIP Is Essential for Progression through Mitosis

Molecular and Cellular Biology ◽

10.1128/mcb.23.5.1666-1673.2003 ◽

2003 ◽

Vol 23 (5) ◽

pp. 1666-1673 ◽

Cited By ~ 51

Author(s):

Eun Ah Cho ◽

Marc J. Prindle ◽

Gregory R. Dressler

Keyword(s):

Cell Proliferation ◽

Dna Repair ◽

Cell Cycle Control ◽

Embryonic Stem ◽

Essential Element ◽

Brct Domain ◽

Transactivation Domain ◽

Mouse Development ◽

Nuclear Condensation ◽

Interacting Protein

ABSTRACT The Pax transactivation domain-interacting protein (PTIP) is a large nuclear protein with multiple BRCT domains that was identified on the basis of its interaction with transcription factors of the Pax and Smad families. To address the function of PTIP during mouse development, we generated a constitutive null allele. Homozygous PTIP mutants are developmentally retarded, disorganized, and embryonic lethal by day 9.5 of embryonic development (E9.5). PTIP mutant cells appear to replicate DNA but show reduced levels of mitosis and widespread cell death by E8.5. DNA damage appears to precede nuclear condensation at E7.5, suggesting a defect in DNA repair. Neither embryonic fibroblast nor embryonic stem cells from PTIP mutants proliferate in culture, suggesting a fundamental defect in cell proliferation. Trophoblast cells from PTIP mutants are more sensitive to DNA-damaging agents. Condensation of chromatin and expression of phospho-histone H3 are also affected in PTIP mutants, and this may underlie the inability of PTIP mutants to progress through mitosis. Given the role of BRCT domain proteins in DNA repair and cell cycle control, we propose that PTIP is an essential element of the cell proliferation machinery, perhaps by functioning in the DNA repair pathways.

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Regulation of E2F1 by BRCT Domain-Containing Protein TopBP1

Molecular and Cellular Biology ◽

10.1128/mcb.23.9.3287-3304.2003 ◽

2003 ◽

Vol 23 (9) ◽

pp. 3287-3304 ◽

Cited By ~ 90

Author(s):

Kang Liu ◽

Fang-Tsyr Lin ◽

J. Michael Ruppert ◽

Weei-Chin Lin

Keyword(s):

Dna Damage ◽

Cell Cycle Progression ◽

Specific Interaction ◽

Dna Damage Checkpoint ◽

Brct Domain ◽

Replication Forks ◽

Direct Role ◽

Dna Topoisomerase ◽

E2f Transcription Factor ◽

Stalled Replication Forks

ABSTRACT The E2F transcription factor integrates cellular signals and coordinates cell cycle progression. Our prior studies demonstrated selective induction and stabilization of E2F1 through ATM-dependent phosphorylation in response to DNA damage. Here we report that DNA topoisomerase IIβ binding protein 1 (TopBP1) regulates E2F1 during DNA damage. TopBP1 contains eight BRCT (BRCA1 carboxyl-terminal) motifs and upon DNA damage is recruited to stalled replication forks, where it participates in a DNA damage checkpoint. Here we demonstrated an interaction between TopBP1 and E2F1. The interaction depended on the amino terminus of E2F1 and the sixth BRCT domain of TopBP1. It was specific to E2F1 and was not observed in E2F2, E2F3, or E2F4. This interaction was induced by DNA damage and phosphorylation of E2F1 by ATM. Through this interaction, TopBP1 repressed multiple activities of E2F1, including transcriptional activity, induction of S-phase entry, and apoptosis. Furthermore, TopBP1 relocalized E2F1 from diffuse nuclear distribution to discrete punctate nuclear foci, where E2F1 colocalized with TopBP1 and BRCA1. Thus, the specific interaction between TopBP1 and E2F1 during DNA damage inhibits the known E2F1 activities but recruits E2F1 to a BRCA1-containing repair complex, suggesting a direct role of E2F1 in DNA damage checkpoint/repair at stalled replication forks.

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