Final published version, 4.94 MB, PDF document
Available under license: CC BY: Creative Commons Attribution 4.0 International License
Final published version
Licence: CC BY: Creative Commons Attribution 4.0 International License
Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
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TY - JOUR
T1 - Distinct regulation of ATM signaling by DNA single-strand breaks and APE1
AU - Zhao, Haichao
AU - Li, Jia
AU - You, Zhongsheng
AU - Lindsay, Howard
AU - Yan, Shan
PY - 2024/8/7
Y1 - 2024/8/7
N2 - In response to DNA double-strand breaks or oxidative stress, ATM-dependentDNA damage response (DDR) is activated to maintain genome integrity.However, it remains elusive whether and how DNA single-strand breaks (SSBs)activate ATM. Here, we provide direct evidence in Xenopus egg extracts thatATM-mediated DDR is activated by a defined SSB structure. Our mechanisticstudies reveal that APE1 promotes the SSB-induced ATM DDR through APE1exonuclease activity and ATM recruitment to SSB sites. APE1 protein can formoligomers to activate the ATM DDR in Xenopus egg extracts in the absence ofDNA and can directly stimulate ATM kinase activity in vitro. Our findings revealdistinct mechanisms of the ATM-dependent DDR activation by SSBs ineukaryotic systems and identify APE1 as a direct activator of ATM kinase.
AB - In response to DNA double-strand breaks or oxidative stress, ATM-dependentDNA damage response (DDR) is activated to maintain genome integrity.However, it remains elusive whether and how DNA single-strand breaks (SSBs)activate ATM. Here, we provide direct evidence in Xenopus egg extracts thatATM-mediated DDR is activated by a defined SSB structure. Our mechanisticstudies reveal that APE1 promotes the SSB-induced ATM DDR through APE1exonuclease activity and ATM recruitment to SSB sites. APE1 protein can formoligomers to activate the ATM DDR in Xenopus egg extracts in the absence ofDNA and can directly stimulate ATM kinase activity in vitro. Our findings revealdistinct mechanisms of the ATM-dependent DDR activation by SSBs ineukaryotic systems and identify APE1 as a direct activator of ATM kinase.
U2 - 10.1038/s41467-024-50836-6
DO - 10.1038/s41467-024-50836-6
M3 - Journal article
VL - 15
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 6517
ER -