Mrg15 null and heterozygous mouse embryonic fibroblasts exhibit DNA-repair defects post exposure to γ ionizing radiation

被引：30

作者：

Garcia, Sandra N. ^{[1
]}

Kirtane, Bhakti M. ^{[2
]}

Podlutsky, Andrej J. ^{[1
]}

Pereira-Smith, Olivia M. ^{[1
]}

Tominaga, Kaoru ^{[1
]}

机构：

[1] Univ Texas Hlth Sci Ctr San Antonio, Dept Cellular & Struct Biol, Barshop Inst Longev & Aging Studies, San Antonio, TX 78245 USA

[2] Natl Inst Res Reprod Hlth, Bombay 400012, Maharashtra, India

来源：

FEBS LETTERS | 2007年 / 581卷 / 27期

关键词：

MORF4; NUA4; Sin3-HDAC; ATM; 53BP1;

D O I：

10.1016/j.febslet.2007.10.017

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：

MORF4-related gene on chromosome 15 (MRG15) is a core component of the NuA4/Tip60 histone acetyltransferase complex that modifies chromatin structure. We here demonstrate that Mrg15 null and heterozygous mouse embryonic fibroblasts exhibit an impaired DNA-damage response post gamma irradiation, when compared to wild-type cells. Defects in DNA-repair and cell growth, and delayed recruitment of repair proteins to sites of damage were observed. Formation of phosphorylated H2AX and 53BP1 foci was delayed in Mrg15 mutant versus wild-type cells following irradiation. These data implicate a novel role for MRG15 in DNA-damage repair in mammalian cells. (C) 2007 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

收藏

页码：5275 / 5281

页数：7

相关论文

共 24 条

[1] Structure of the chromatin binding (chromo) domain from mouse modifier protein 1 [J].

Ball, LJ ;

Murzina, NV ;

Broadhurst, RW ;

Raine, ARC ;

Archer, SJ ;

Stott, FJ ;

Murzin, AG ;

Singh, PB ;

Domaille, PJ ;

Laue, ED .

EMBO JOURNAL, 1997, 16 (09) :2473-2481

[2]

Bertram MJ, 1999, MOL CELL BIOL, V19, P1479

[3] Self-association of chrome domain peptides [J].

Cowell, IG ;

Austin, CA .

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEIN STRUCTURE AND MOLECULAR ENZYMOLOGY, 1997, 1337 (02) :198-206

[4] Dynamics of chromatin during the repair of DNA double-strand breaks [J].

Downs, JA ;

Côté, J .

CELL CYCLE, 2005, 4 (10) :1373-1376

[5] Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans [J].

Doyon, Y ;

Selleck, W ;

Lane, WS ;

Tan, S ;

Cöté, J .

MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (05) :1884-1896

[6] The yeast NuA4 and Drosophila MSL complexes contain homologous subunits important for transcription regulation [J].

Eisen, A ;

Utley, RT ;

Nourani, A ;

Allard, S ;

Schmidt, P ;

Lane, WS ;

Lucchesi, JC ;

Côté, J .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (05) :3484-3491

[7] Involvement of human MOF in ATM function [J].

Gupta, A ;

Sharma, GG ;

Young, CSH ;

Agarwal, M ;

Smith, ER ;

Paull, TT ;

Lucchesi, JC ;

Khanna, KK ;

Ludwig, T ;

Pandita, TK .

MOLECULAR AND CELLULAR BIOLOGY, 2005, 25 (12) :5292-5305

[8] Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions [J].

Kusch, T ;

Florens, L ;

MacDonald, WH ;

Swanson, SK ;

Glaser, RL ;

Yates, JR ;

Abmayr, SM ;

Washburn, MP ;

Workman, JL .

SCIENCE, 2004, 306 (5704) :2084-2087

[9] ATM activation and DNA damage response [J].

Lavin, Martin F. ;

Kozlov, Sergei .

CELL CYCLE, 2007, 6 (08) :931-942

[10] H2AX phosphorylation within the G1 phase after UV irradiation depends on nucleotide excision repair and not DNA double-strand breaks [J].

Marti, Thomas M. ;

Hefner, Eli ;

Feeney, Luzviminda ;

Natale, Valerie ;

Cleaver, James E. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (26) :9891-9896