ArticleMolecular and cellular biology2010
BRCT domain interactions with phospho-histone H2A target Crb2 to chromatin at double-strand breaks and maintain the DNA damage checkpoint.
Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Multiple DNA repair pathways contribute to MMS-induced post-replicative DNA synthesis inmicroPublication biology · 2023Article
- Determinants of RPA megafoci localization to the nuclear periphery in response to replication stress.G3 (Bethesda, Md.) · 2022Article
- Checkpoint functions of RecQ helicases at perturbed DNA replication fork.Current genetics · 2021Review
- Review
- Livin Regulates H2A.XFrontiers in oncology · 2019Article
- Multi-BRCT Domain Protein Brc1 Links Rhp18/Rad18 and γH2A To Maintain Genome Stability during S Phase.Molecular and cellular biology · 2017Article
- Review
- Miltirone exhibits antileukemic activity by ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction pathways.Scientific reports · 2016Article
- Critical Function of γH2A in S-Phase.PLoS genetics · 2015Article
- Dimerization Mediated by a Divergent Forkhead-associated Domain Is Essential for the DNA Damage and Spindle Functions of Fission Yeast Mdb1.The Journal of biological chemistry · 2015Article
- Ubiquitin-H2AX fusions render 53BP1 recruitment to DNA damage sites independent of RNF8 or RNF168.Cell cycle (Georgetown, Tex.) · 2015Article
- Mdb1, a fission yeast homolog of human MDC1, modulates DNA damage response and mitotic spindle function.PloS one · 2014Article
- Double-strand break repair: 53BP1 comes into focus.Nature reviews. Molecular cell biology · 2014Review
- γH2A-binding protein Brc1 affects centromere function in fission yeast.Molecular and cellular biology · 2013Article
- Perceiving the epigenetic landscape through histone readers.Nature structural & molecular biology · 2012Review
- Replication fork collapse and genome instability in a deoxycytidylate deaminase mutant.Molecular and cellular biology · 2012Article
- Multiple phosphorylation of Rad9 by CDK is required for DNA damage checkpoint activation.Cell cycle (Georgetown, Tex.) · 2012Article
- A new method to efficiently induce a site-specific double-strand break in the fission yeast Schizosaccharomyces pombe.Yeast (Chichester, England) · 2012Article
- The demise of a TUDOR under stress opens a chromatin link to 53BP1.The EMBO journal · 2012Article
- Dynamics of DNA damage response proteins at DNA breaks: a focus on protein modifications.Genes & development · 2011Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Relocalization of checkpoint proteins to chromatin flanking DNA double-strand breaks (DSBs) is critical for cellular responses to DNA damage. Schizosaccharomyces pombe Crb2, which mediates Chk1 activation by Rad3(ATR), forms ionizing radiation-induced nuclear foci (IRIF). Crb2 C-terminal BRCT domains (BRCT(2)) bind histone H2A phosphorylated at a C-terminal SQ motif by Tel1(ATM) and Rad3(ATR), although the functional significance of this interaction is controversial. Here, we show that polar interactions of Crb2 serine-548 and lysine-619 with the phosphate group of phospho-H2A (γ-H2A) are critical for Crb2 IRIF formation and checkpoint function. Mutations of these BRCT(2) domain residues have additive effects when combined in a single allele. Combining either mutation with an allele that eliminates the threonine-215 cyclin-dependent kinase phosphorylation site completely abrogates Crb2 IRIF and function. We propose that cooperative phosphate interactions in the BRCT(2) γ-H2A-binding pocket of Crb2, coupled with tudor domain interactions with lysine-20 dimethylation of histone H4, facilitate stable recruitment of Crb2 to chromatin surrounding DSBs, which in turn mediates efficient phosphorylation of Chk1 that is required for a sustained checkpoint response. This mechanism of cooperative interactions with the γ-H2A/X phosphate is likely conserved in S. pombe Brc1 and human Mdc1 genome maintenance proteins.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.