PTEN in the maintenance of genome integrity: From DNA replication to chromosome segregation

被引：54
作者：
Hou, Sheng-Qi [1 ]
Ouyang, Meng [1 ]
Brandmaier, Andrew [1 ]
Hao, Hongbo [1 ]
Shen, Wen H. [1 ]
机构：
[1] Cornell Univ, Weill Cornell Med, Dept Radiat Oncol, New York, NY 10021 USA
来源：
BIOESSAYS | 2017年 / 39卷 / 10期
基金：
美国国家卫生研究院;
关键词：
checkpoint; chromosome segregation; DNA replication; genome; mitotic spindle; PTEN; TUMOR-SUPPRESSOR GENE; NUCLEAR PTEN; CELL-CYCLE; HOMOLOGOUS RECOMBINATION; PROSTATE-CANCER; DOWN-REGULATION; PHOSPHATASE; CHECKPOINT; PROTEIN; DAMAGE;
D O I：
10.1002/bies.201700082
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
Faithful DNA replication and accurate chromosome segregation are the key machineries of genetic transmission. Disruption of these processes represents a hallmark of cancer and often results from loss of tumor suppressors. PTEN is an important tumor suppressor that is frequently mutated or deleted in human cancer. Loss of PTEN has been associated with aneuploidy and poor prognosis in cancer patients. In mice, Pten deletion or mutation drives genomic instability and tumor development. PTEN deficiency induces DNA replication stress, confers stress tolerance, and disrupts mitotic spindle architecture, leading to accumulation of structural and numerical chromosome instability. Therefore, PTEN guards the genome by controlling multiple processes of chromosome inheritance. Here, we summarize current understanding of the PTEN function in promoting high-fidelity transmission of genetic information. We also discuss the PTEN pathways of genome maintenance and highlight potential targets for cancer treatment.
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页数：9
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