A New BRCT Binding Mode in TopBP1-BLM Helicase Interaction
نویسندگان
چکیده
منابع مشابه
TopBP1 Interacts with BLM to Maintain Genome Stability but Is Dispensable for Preventing BLM Degradation
The Bloom syndrome helicase BLM and topoisomerase-IIβ-binding protein 1 (TopBP1) are key regulators of genome stability. It was recently proposed that BLM phosphorylation on Ser338 mediates its interaction with TopBP1, to protect BLM from ubiquitylation and degradation (Wang et al., 2013). Here, we show that the BLM-TopBP1 interaction does not involve Ser338 but instead requires BLM phosphoryla...
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The diverse roles of TopBP1 in DNA replication and checkpoint signaling are associated with the scaffolding ability of TopBP1 to initiate various protein-protein interactions. The recognition of the BACH1/FANCJ helicase by TopBP1 is critical for the activation of the DNA replication checkpoint at stalled replication forks and is facilitated by the C-terminal tandem BRCT7/8 domains of TopBP1 and...
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Bloom's syndrome is a rare autosomal recessive genetic disorder characterized by chromosomal aberrations, genetic instability, and cancer predisposition, all of which may be the result of abnormal signal transduction during DNA damage recognition. Here, we show that BLM is an intermediate responder to stalled DNA replication forks. BLM colocalized and physically interacted with the DNA damage r...
متن کاملStructural insights into recognition of MDC1 by TopBP1 in DNA replication checkpoint control.
Activation of the DNA replication checkpoint by the ATR kinase requires protein interactions mediated by the ATR-activating protein, TopBP1. Accumulation of TopBP1 at stalled replication forks requires the interaction of TopBP1 BRCT5 with the phosphorylated SDT repeats of the adaptor protein MDC1. Here, we present the X-ray crystal structures of the tandem BRCT4/5 domains of TopBP1 free and in ...
متن کاملTopBP1 contains a transcriptional activation domain suppressed by two adjacent BRCT domains.
TopBP1 has eight BRCT [BRCA1 (breast-cancer susceptibility gene 1) C-terminus] domains and is involved in initiating DNA replication, and DNA damage checkpoint signalling and repair. Several BRCT-domain-containing proteins involved in mediating DNA repair have transcriptional regulatory domains, and as demonstrated for BRCA1 these regulatory domains are important in mediating the functions of t...
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ژورنال
عنوان ژورنال: Structure
سال: 2017
ISSN: 0969-2126
DOI: 10.1016/j.str.2017.09.011