Human CtIP promotes DNA end resection

@article{Sartori2007HumanCP,
  title={Human CtIP promotes DNA end resection},
  author={Alessandro A. Sartori and Claudia Lukas and Julia Coates and Martin Mistrik and Shuang Fu and Jiri Bartek and Richard J. Baer and Jiri Lukas and Stephen P. Jackson},
  journal={Nature},
  year={2007},
  volume={450},
  pages={509-514}
}
In the S and G2 phases of the cell cycle, DNA double-strand breaks (DSBs) are processed into single-stranded DNA, triggering ATR-dependent checkpoint signalling and DSB repair by homologous recombination. Previous work has implicated the MRE11 complex in such DSB-processing events. Here, we show that the human CtIP (RBBP8) protein confers resistance to DSB-inducing agents and is recruited to DSBs exclusively in the S and G2 cell-cycle phases. Moreover, we reveal that CtIP is required for DSB… 
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CtIP links DNA double-strand break sensing to resection.

Mre11 regulates CtIP–dependent double strand break repair by interaction with CDK2

It is shown that, in human and mouse, Mre11 controls these events through a direct interaction with CDK2 that is required for CtIP phosphorylation and BRCA1 interaction in normally dividing cells.

CtIP Protein Dimerization Is Critical for Its Recruitment to Chromosomal DNA Double-stranded Breaks*

It is suggested that CtIP dimer formation is essential for its recruitment to DSBs on chromatin upon DNA damage, in addition to the C-terminal conserved domains critical for CtIP function.

Regulation of DNA-end resection by hnRNPU-like proteins promotes DNA double-strand break signaling and repair.

N Terminus of CtIP Is Critical for Homologous Recombination-mediated Double-strand Break Repair*

This work demonstrates that besides the known conserved C terminus, the N terminus of CtIP protein is also required in DSB end resection and DNA damage-induced G2/M checkpoint control and shows that both termini ofCtIP can interact with the MRN complex and that the N Terminus plays a critical role in targeting CtIP to sites of DNA breaks.

The Human SRCAP Chromatin Remodeling Complex Promotes DNA-End Resection

And-1 coordinates with CtIP for efficient homologous recombination and DNA damage checkpoint maintenance

It is established that And-1, a replisome component, promotes DNA-end resection and DNA repair by homologous recombination and is critically required for sustained ATR–CHK1 checkpoint signaling and for maintaining both the intra-S- and G2-phase checkpoints.

EXD2 promotes homologous recombination by facilitating DNA-end resection

It is established that EXD2 stimulates both short- and long-range DSB resection, and thus, together with MRE11, is required for efficient HR.

Phosphorylation-regulated binding of Ctp1 to Nbs1 is critical for repair of DNA double-strand breaks

New data is presented that further characterize the cellular consequences of mutating CK2 phosphorylation motifs of Ctp1, including data showing that these sites are critical for meiosis.

DNA helicases Sgs1 and BLM promote DNA double-strand break resection.

It is revealed that in the absence of exonuclease Exo1 activity, deletion or mutation of the Saccharomyces cerevisiae RecQ-family helicase, Sgs1, causes pronounced hypersensitivity to DSB-inducing agents, and it is established that this reflects severely compromised DSB resection, deficient DNA damage signaling, and strongly impaired HR-mediated repair.
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References

SHOWING 1-10 OF 52 REFERENCES

Choreography of the DNA Damage Response Spatiotemporal Relationships among Checkpoint and Repair Proteins

DNA end resection, homologous recombination and DNA damage checkpoint activation require CDK1

It is reported that DNA damage checkpoint activation by a DSB requires the cyclin-dependent kinase CDK1 (Cdc28) in budding yeast, andCDK1 is also required for DSB-induced homologous recombination at any cell cycle stage.

Multiple Endonucleases Function to Repair Covalent Topoisomerase I Complexes in Saccharomyces cerevisiae

Genetic analysis revealed that the flap endonucleases Slx4 and Sae2 represent new pathways parallel to Tdp1, Rad1, and Mus81 that protect cells from camptothecin toxicity.

Spatial organization of the mammalian genome surveillance machinery in response to DNA strand breaks

It is proposed that subclassification of DSB regulators according to their residence sites provides a useful framework for understanding their involvement in diverse processes of genome surveillance.

The Functions of Budding Yeast Sae2 in the DNA Damage Response Require Mec1- and Tel1-Dependent Phosphorylation

The Saccharomyces cerevisiae Sae2 protein, known to be involved in processing meiotic and mitotic double-strand breaks, is required for proper recovery from checkpoint-mediated cell cycle arrest after DNA damage and is phosphorylated periodically during the unperturbed cell cycle and in response to DNA damage.

MRE11/RAD50/NBS1: complex activities

New data suggest that the Mre11 complex can directly activate the ATM checkpoint kinase at DNA breaks, identifying the M re11 complex as an architectural and mechanistic keystone of cellular response events emerging from DNA breaks.

Distinct spatiotemporal dynamics of mammalian checkpoint regulators induced by DNA damage

A dynamic nature of Nbs1 interaction with DSB lesions is unraveled and Chk2 is identified as a candidate transmitter of the checkpoint signal, allowing for a coordinated pan-nuclear response to focal DNA damage.

ATM regulates ATR chromatin loading in response to DNA double-strand breaks

Experimental evidence is provided of an active cross talk between ATM and ATR signaling pathways in response to DNA damage, which places ATM activity upstream of ATR recruitment to IR-damaged chromatin.

DNA Double-Strand Breaks

Although rearranged Vλ genes are preferred targets of SHM, it is found that germinal center B cells of AID-proficient and -deficient Vλ1-expressing GC B cells display a similar frequency, distribution, and sequence preference of DSBs in rearranged and also in germline Vλ 1 genes.

The Mre11 complex and ATM: a two-way functional interaction in recognising and signaling DNA double strand breaks.

...