3t7k
From Proteopedia
Complex structure of Rtt107p and phosphorylated histone H2A
Structural highlights
Function[RT107_YEAST] Required for resumption of chromosome replication after DNA damage, specifically in S phase. Is recruited to chromatin in the presence of RTT109 and RTT101 in response to stalled replication forks and acts as a scaffold during DNA repair.[1] [2] [H2A1_YEAST] Core component of nucleosome which plays a central role in DNA double strand break (DSB) repair. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.[3] [4] [5] [6] Publication Abstract from PubMedRtt107 (regulator of Ty1 transposition 107; Esc4) is a DNA repair protein from Saccharomyces cerevisiae that can restore stalled replication forks following DNA damage. There are six BRCT (BRCA1 C-terminal) domains in Rtt107 that act as binding sites for other recruited proteins during DNA repair. Several Rtt107 binding partners have been identified, including Slx4, Rtt101, Rad55, and the Smc5/6 (structural maintenance of chromosome) protein complex. Rtt107 can reportedly be recruited to chromatin in the presence of Rtt101 and Rtt109 upon DNA damage, but the chromatin-binding site of Rtt107 has not been identified. Here, we report our investigation of the interaction between phosphorylated histone H2A (gammaH2A) and the C-terminal tandem BRCT repeats (BRCT(5)-BRCT(6)) of Rtt107. The crystal structures of BRCT(5)-BRCT(6) alone and in a complex with gammaH2A reveal the molecular basis of the Rtt107-gammaH2A interaction. We used in vitro mutagenesis and a fluorescence polarization assay to confirm the location of the Rtt107 motif that is crucial for this interaction. In addition, these assays indicated that this interaction requires the phosphorylation of H2A. An in vivo phenotypic analysis in yeast demonstrated the critical role of BRCT(5)-BRCT(6) and its interaction with gammaH2A during the DNA damage response. Our results shed new light on the molecular mechanism by which Rtt107 is recruited to chromatin in response to stalled DNA replication forks. Structure of C-terminal tandem BRCT repeats of Rtt107 protein reveals critical role in interaction with phosphorylated histone H2A during DNA damage repair.,Li X, Liu K, Li F, Wang J, Huang H, Wu J, Shi Y J Biol Chem. 2012 Mar 16;287(12):9137-46. Epub 2012 Jan 19. PMID:22262834[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Baker's yeast | Large Structures | Li, F | Li, X | Shi, Y | Wu, J | Brct | Dna repair | Phospho-peptide | Protein binding
