Your browser doesn't support javascript.
loading
Replication Stress Induces ATR/CHK1-Dependent Nonrandom Segregation of Damaged Chromosomes.
Xing, Meichun; Zhang, Fengjiao; Liao, Hongwei; Chen, Sisi; Che, Luanqing; Wang, Xiaohui; Bao, Zhengqiang; Ji, Fang; Chen, Gaoying; Zhang, Huihui; Li, Wen; Chen, Zhihua; Liu, Ying; Hickson, Ian D; Shen, Huahao; Ying, Songmin.
Afiliação
  • Xing M; Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.
  • Zhang F; Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.
  • Liao H; Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.
  • Chen S; Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.
  • Che L; Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Wang X; Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.
  • Bao Z; Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.
  • Ji F; Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.
  • Chen G; Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.
  • Zhang H; Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China.
  • Li W; Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Chen Z; Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China.
  • Liu Y; Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.
  • Hickson ID; Center for Chromosome Stability and Center for Healthy Aging, Department of Cellular and Molecular Medicine, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark. Electronic address: iandh@sund.ku.dk.
  • Shen H; Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, China; State Key Laboratory of Respiratory Diseases, Guangzhou, Guangdong 510120, China.
  • Ying S; Department of Pharmacology and Department of Respiratory and Critical Care Medicine of the Second Affiliated Hospital, Zhejiang University School of Medicine, Key Laboratory of Respiratory Disease of Zhejiang Province, Hangzhou 310009, China. Electronic address: yings@zju.edu.cn.
Mol Cell ; 78(4): 714-724.e5, 2020 05 21.
Article em En | MEDLINE | ID: mdl-32353258
ABSTRACT
Nonrandom DNA segregation (NDS) is a mitotic event in which sister chromatids carrying the oldest DNA strands are inherited exclusively by one of the two daughter cells. Although this phenomenon has been observed across various organisms, the mechanism and physiological relevance of this event remain poorly defined. Here, we demonstrate that DNA replication stress can trigger NDS in human cells. This biased inheritance of old template DNA is associated with the asymmetric DNA damage response (DDR), which derives at least in part from telomeric DNA. Mechanistically, we reveal that the ATR/CHK1 signaling pathway plays an essential role in mediating NDS. We show that this biased segregation process leads to cell-cycle arrest and cell death in damaged daughter cells inheriting newly replicated DNA. These data therefore identify a key role for NDS in the maintenance of genomic integrity within cancer cell populations undergoing replication stress due to oncogene activation.
Assuntos
Palavras-chave
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dano ao DNA / Cromossomos Humanos / Replicação do DNA / Proteínas Mutadas de Ataxia Telangiectasia / Quinase 1 do Ponto de Checagem / Mitose Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Dano ao DNA / Cromossomos Humanos / Replicação do DNA / Proteínas Mutadas de Ataxia Telangiectasia / Quinase 1 do Ponto de Checagem / Mitose Limite: Humans Idioma: En Ano de publicação: 2020 Tipo de documento: Article