DNMT1 knockout delivers a strong blow to genome stability and cell viability

被引：44

作者：

Brown, Kevin D.

Robertson, Keith D.

机构：

[1] Univ Florida, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA

[2] Univ Florida, Shands Canc Ctr, Gainesville, FL 32610 USA

来源：

NATURE GENETICS | 2007年 / 39卷 / 03期

关键词：

D O I：

10.1038/ng0307-289

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

The DNA methyltransferase DNMT1 is essential for cell viability in various mouse models, but gene targeting in human tumor cells results in a viable line. This dilemma has now been resolved using a new human DNMT1 knockout line, although new questions arise as to the full extent of DNMT1 function in maintaining genome integrity.

引用

收藏

页码：289 / 290

页数：3

相关论文

共 15 条

[1] DNA damage activates ATM through intermolecular autophosphorylation and dimer dissociation [J].

Bakkenist, CJ ;

Kastan, MB .

NATURE, 2003, 421 (6922) :499-506

[2] Requirement for p53 and p21 to sustain G2 arrest after DNA damage [J].

Bunz, F ;

Dutriaux, A ;

Lengauer, C ;

Waldman, T ;

Zhou, S ;

Brown, JP ;

Sedivy, JM ;

Kinzler, KW ;

Vogelstein, B .

SCIENCE, 1998, 282 (5393) :1497-1501

[3] Complete inactivation of DNMT1 leads to mitotic catastrophe in human cancer cells [J].

Chen, Taiping ;

Hevi, Sarah ;

Gay, Frederique ;

Tsujimoto, Naomi ;

He, Timothy ;

Zhang, Bailin ;

Ueda, Yoshihide ;

Li, En .

NATURE GENETICS, 2007, 39 (03) :391-396

[4] Human DNA (cytosine-5) methyltransferase PCNA complex as a target for p21(WAF1) [J].

Chuang, LSH ;

Ian, HI ;

Koh, TW ;

Ng, HH ;

Xu, GL ;

Li, BFL .

SCIENCE, 1997, 277 (5334) :1996-2000

[5] Identification of DNMT1 (DNA methyltransferase 1) hypomorphs in somatic knockouts suggests an essential role for DNMT1 in cell survival [J].

Egger, Gerda ;

Jeong, Shinwu ;

Escobar, Sonia G. ;

Cortez, Connie C. ;

Li, Tony W. H. ;

Saito, Yoshimasa ;

Yoo, Christine B. ;

Jones, Peter A. ;

Liang, Gangning .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (38) :14080-14085

[6] Human maintenance DNA (cytosine-5)-methyltransferase and p53 modulate expression of p53-repressed promoters [J].

Estève, PO ;

Chin, HG ;

Pradhan, S .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (04) :1000-1005

[7] Loss of genomic methylation causes p53-dependent apoptosis and epigenetic deregulation [J].

Jackson-Grusby, L ;

Beard, C ;

Possemato, R ;

Tudor, M ;

Fambrough, D ;

Csankovszki, G ;

Dausman, T ;

Lee, P ;

Wilson, C ;

Lander, E ;

Jaenisch, R .

NATURE GENETICS, 2001, 27 (01) :31-39

[8] Genetic disruption of cytosine DNA methyltransferase enzymes induces chromosomal instability in human cancer cells [J].

Karpf, AR ;

Matsui, S .

CANCER RESEARCH, 2005, 65 (19) :8635-8639

[9] TARGETED MUTATION OF THE DNA METHYLTRANSFERASE GENE RESULTS IN EMBRYONIC LETHALITY [J].

LI, E ;

BESTOR, TH ;

JAENISCH, R .

CELL, 1992, 69 (06) :915-926

[10] Recruitment of DNA methyltransferase I to DNA repair sites [J].

Mortusewicz, O ;

Schermelleh, L ;

Walter, J ;

Cardoso, MC ;

Leonhardt, H .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (25) :8905-8909