STAG2 Regulates Homologous Recombination Repair and Sensitivity to ATM Inhibition

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Abstract: Stromal antigen 2 (STAG2), a subunit of the cohesin complex, is recurrently mutated in various tumors. However, the role of STAG2 in DNA repair and its therapeutic implications are largely unknown. Here it is reported that knockout of STAG2 results in increased double‐stranded breaks (DSBs) and chromosomal aberrations by reducing homologous recombination (HR) repair, and confers hypersensitivity to inhibitors of ataxia telangiectasia mutated (ATMi), Poly ADP Ribose Polymerase (PARPi), or the combination of both. Of note, the impaired HR by STAG2‐deficiency is mainly attributed to the restored expression of KMT5A, which in turn methylates H4K20 (H4K20me0) to H4K20me1 and thereby decreases the recruitment of BRCA1‐BARD1 to chromatin. Importantly, STAG2 expression correlates with poor prognosis of cancer patients. STAG2 is identified as an important regulator of HR and a potential therapeutic strategy for STAG2‐mutant tumors is elucidated.

Standort: Deutsche Nationalbibliothek Frankfurt am Main

Umfang: Online-Ressource

Sprache: Englisch

Erschienen in: STAG2 Regulates Homologous Recombination Repair and Sensitivity to ATM Inhibition ; day:20 ; month:11 ; year:2023 ; extent:16
Advanced science ; (20.11.2023) (gesamt 16)

Urheber: Zhou, Jie
Nie, Run‐Cong
He, Zhang‐Ping
Cai, Xiao‐Xia
Chen, Jie‐Wei
Lin, Wen‐ping
Yin, Yi‐Xin
Xiang, Zhi‐Cheng
Zhu, Tian‐Chen
Xie, Juan‐Juan
Zhang, You‐Cheng
Wang, Xin
Lin, Peng
Xie, Dan
D'Andrea, Alan D.
Cai, Mu‐Yan

DOI: 10.1002/advs.202302494

URN: urn:nbn:de:101:1-2023112114472191813185

Rechteinformation: Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.

Letzte Aktualisierung: 15.08.2025, 07:27 MESZ

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Beteiligte

Zhou, Jie
Nie, Run‐Cong
He, Zhang‐Ping
Cai, Xiao‐Xia
Chen, Jie‐Wei
Lin, Wen‐ping
Yin, Yi‐Xin
Xiang, Zhi‐Cheng
Zhu, Tian‐Chen
Xie, Juan‐Juan
Zhang, You‐Cheng
Wang, Xin
Lin, Peng
Xie, Dan
D'Andrea, Alan D.
Cai, Mu‐Yan

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STAG2 Regulates Homologous Recombination Repair and Sensitivity to ATM Inhibition

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