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Involvement of ATM in homologous recombination after end resection and RAD51 nucleofilament formation.

Bakr A, Oing C, Köcher S, Borgmann K, Dornreiter I, Petersen C, Dikomey E, Mansour WY - Nucleic Acids Res. (2015)

Bottom Line: Here we show for the first time that ATM is also needed for later steps in HR after RAD51 nucleofilament formation.Moreover, we demonstrated that ATR can partly compensate for the deficiency in early, but not in later, steps of HR upon ATM inhibition.Taken together, we describe here for the first time that ATM is needed not only for the initiation but also for the completion of HR.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.

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Related in: MedlinePlus

Proposed model for the role of ATM in HR. ATM is indeed required for the presynapsis stage of HR: (i) to phosphorylate and remove KAP1, facilitating the recruitment of HR proteins; (ii) to regulate the end resection step by stimulating the nucleolytic activity of MRE11/CtIP to generate 3′-ssDNA overhangs and facilitate RAD51 nucleofilament formation; (iii) in addition, we describe here for the first time that ATM is also required for HR after RAD51 nucleofilament formation. In the absence of ATM, ATR can only participate in the early steps of HR, possibly through the stimulation of end resection and RAD51 nucleofilament formation.
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Figure 7: Proposed model for the role of ATM in HR. ATM is indeed required for the presynapsis stage of HR: (i) to phosphorylate and remove KAP1, facilitating the recruitment of HR proteins; (ii) to regulate the end resection step by stimulating the nucleolytic activity of MRE11/CtIP to generate 3′-ssDNA overhangs and facilitate RAD51 nucleofilament formation; (iii) in addition, we describe here for the first time that ATM is also required for HR after RAD51 nucleofilament formation. In the absence of ATM, ATR can only participate in the early steps of HR, possibly through the stimulation of end resection and RAD51 nucleofilament formation.

Mentions: The current work reports for the first time that ATM is involved in HR not only in presynapsis through the stimulation of DSB end resection, but importantly also in the later steps of HR after end resection and RAD51 nucleofilament formation (Figure 7).


Involvement of ATM in homologous recombination after end resection and RAD51 nucleofilament formation.

Bakr A, Oing C, Köcher S, Borgmann K, Dornreiter I, Petersen C, Dikomey E, Mansour WY - Nucleic Acids Res. (2015)

Proposed model for the role of ATM in HR. ATM is indeed required for the presynapsis stage of HR: (i) to phosphorylate and remove KAP1, facilitating the recruitment of HR proteins; (ii) to regulate the end resection step by stimulating the nucleolytic activity of MRE11/CtIP to generate 3′-ssDNA overhangs and facilitate RAD51 nucleofilament formation; (iii) in addition, we describe here for the first time that ATM is also required for HR after RAD51 nucleofilament formation. In the absence of ATM, ATR can only participate in the early steps of HR, possibly through the stimulation of end resection and RAD51 nucleofilament formation.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4381069&req=5

Figure 7: Proposed model for the role of ATM in HR. ATM is indeed required for the presynapsis stage of HR: (i) to phosphorylate and remove KAP1, facilitating the recruitment of HR proteins; (ii) to regulate the end resection step by stimulating the nucleolytic activity of MRE11/CtIP to generate 3′-ssDNA overhangs and facilitate RAD51 nucleofilament formation; (iii) in addition, we describe here for the first time that ATM is also required for HR after RAD51 nucleofilament formation. In the absence of ATM, ATR can only participate in the early steps of HR, possibly through the stimulation of end resection and RAD51 nucleofilament formation.
Mentions: The current work reports for the first time that ATM is involved in HR not only in presynapsis through the stimulation of DSB end resection, but importantly also in the later steps of HR after end resection and RAD51 nucleofilament formation (Figure 7).

Bottom Line: Here we show for the first time that ATM is also needed for later steps in HR after RAD51 nucleofilament formation.Moreover, we demonstrated that ATR can partly compensate for the deficiency in early, but not in later, steps of HR upon ATM inhibition.Taken together, we describe here for the first time that ATM is needed not only for the initiation but also for the completion of HR.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Radiobiology & Experimental Radiooncology, University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany.

Show MeSH
Related in: MedlinePlus