The ATM-Chk2 and ATR-Chk1 pathways in DNA damage signaling and cancer.
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Additional excerpts
...recombination (HR) (Smith et al., 2010)....
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...Oncogene recombination (HR) (Smith et al., 2010)....
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Cites background from "The ATM-Chk2 and ATR-Chk1 pathways ..."
...Development of highly specific inhibitors of ATM, Chk1, and Chk2 has made promising progress (Smith et al. 2010)....
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Cites background from "The ATM-Chk2 and ATR-Chk1 pathways ..."
...For example, the E3 ubiquitin ligase Smurf1 determines cell apoptosis rates downstream of DNA damage–induced ATR–Chk1 signaling by promoting the death of transformed cells [107, 108]....
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643 citations
Cites background from "The ATM-Chk2 and ATR-Chk1 pathways ..."
...This in turn impairs CDC25 family member activation of cyclin dependent kinases (CDKs) and G1/S and G2/M transitions [94]....
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References
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"The ATM-Chk2 and ATR-Chk1 pathways ..." refers background in this paper
...The exact nature of the primary activating signal that triggers ATM autophosphorylation remains unknown; however, it does not appear to be limited to the immediate vicinity of the damage and may be linked to long-range alterations in chromatin structure (Bakkenist and Kastan, 2003)....
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..., 2006), although its modification is tightly linked to ATM activation under most circumstances (Bakkenist and Kastan, 2003)....
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...In response to DSBs, inactive ATM homodimers are rapidly induced to autophosphorylate in trans, resulting in dissociation to form partially active monomers (Bakkenist and Kastan, 2003)....
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...Serine (S) S1981 was the first autophosphorylation site to be identified; however, this residue is not essential for ATM function, at least in mice (Pellegrini et al., 2006), although its modification is tightly linked to ATM activation under most circumstances (Bakkenist and Kastan, 2003)....
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