Hdac3 Is Essential for the Maintenance of Chromatin Structure and Genome Stability

被引：305

作者：

Bhaskara, Srividya ^{[1
]}

Knutson, Sarah K. ^{[1
]}

Jiang, Guochun ^{[2
,3
]}

Chandrasekharan, Mahesh B. ^{[1
]}

Wilson, Andrew J. ^{[4
]}

Zheng, Siyuan ^{[5
,6
]}

Yenamandra, Ashwini ^{[7
]}

Locke, Kimberly ^{[8
]}

Yuan, Jia-ling ^{[1
]}

Bonine-Summers, Alyssa R. ^{[1
]}

Wells, Christina E. ^{[1
]}

Kaiser, Jonathan F. ^{[1
]}

Washington, M. Kay ^{[9
]}

Zhao, Zhongming ^{[3
,6
,9
]}

Wagner, Florence F. ^{[10
]}

Sun, Zu-Wen ^{[1
,9
]}

Xia, Fen ^{[2
]}

Holson, Edward B. ^{[10
]}

Khabele, Dineo ^{[3
,4
,9
]}

Hiebert, Scott W. ^{[1
,9
]}

机构：

[1] Vanderbilt Univ, Dept Biochem, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Med Ctr, Dept Radiat Oncol, Nashville, TN 37212 USA

[3] Vanderbilt Univ, Med Ctr, Dept Canc Biol, Nashville, TN 37212 USA

[4] Vanderbilt Univ, Med Ctr, Dept Obstet & Gynecol, Div Gynecol Oncol, Nashville, TN 37212 USA

[5] Vanderbilt Univ, Sch Med, Dept Biomed Informat, Nashville, TN 37232 USA

[6] Vanderbilt Univ, Sch Med, Bioinformat Resource Ctr, Nashville, TN 37232 USA

[7] Vanderbilt Univ, Dept Pathol, Nashville, TN 37232 USA

[8] PathGrp, Nashville, TN 37211 USA

[9] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA

[10] MIT & Harvard, Broad Inst, Cambridge, MA 02142 USA

来源：

CANCER CELL | 2010年 / 18卷 / 05期

基金：

美国国家卫生研究院;

关键词：

NUCLEAR HORMONE-RECEPTORS; DNA-DAMAGE DETECTION; DOUBLE-STRAND BREAKS; HISTONE DEACETYLASE; HEPATOCELLULAR-CARCINOMA; SACCHAROMYCES-CEREVISIAE; PROSTATE-CANCER; CO-REPRESSOR; COLON-CANCER; IN-VITRO;

D O I：

10.1016/j.ccr.2010.10.022

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Hdac3 is essential for efficient DNA replication and DNA damage control. Deletion of Hdac3 impaired DNA repair and greatly reduced chromatin compaction and heterochromatin content. These defects corresponded to increases in histone H3K9,K14ac; H4K5ac; and H4K12ac in late S phase of the cell cycle, and histone deposition marks were retained in quiescent Hdac3-null cells. Liver-specific deletion of Hdac3 culminated in hepatocellular carcinoma. Whereas HDAC3 expression was downregulated in only a small number of human liver cancers, the mRNA levels of the HDAC3 cofactor NCOR1 were reduced in one-third of these cases. siRNA targeting of NCOR1 and SMRT (NCOR2) increased H4K5ac and caused DNA damage, indicating that the HDAC3/NCOR/SMRT axis is critical for maintaining chromatin structure and genomic stability.

引用

页码：436 / 447

页数：12

共 63 条

[1] DNA damage detection and repair pathways - Recent advances with inhibitors of checkpoint kinases in cancer therapy
Ashwell, Susan
Zabludoff, Sonya
[J]. CLINICAL CANCER RESEARCH, 2008, 14 (13) : 4032 - 4037
[2] HP1-β is required for development of the cerebral neocortex and neuromuscular junctions
Aucott, Rebecca
Bullwinkel, Joern
Yu, Yang
Shi, Wei
Billur, Mustafa
Brown, Jeremy P.
Menzel, Ursula
Kioussis, Dimitris
Wang, Guozheng
Reisert, Ingrid
Weimer, Joerg
Pandita, Raj K.
Sharma, Girdhar G.
Pandita, Tej K.
Fundele, Reinald
Singh, Prim B.
[J]. JOURNAL OF CELL BIOLOGY, 2008, 183 (04) : 597 - 606
[3] HP1-β mobilization promotes chromatin changes that initiate the DNA damage response
Ayoub, Nabieh
Jeyasekharan, Anand D.
Bernal, Juan A.
Venkitaraman, Ashok R.
[J]. NATURE, 2008, 453 (7195) : 682 - U14
[4] NCBI GEO: archive for high-throughput functional genomic data
Barrett, Tanya
Troup, Dennis B.
Wilhite, Stephen E.
Ledoux, Pierre
Rudnev, Dmitry
Evangelista, Carlos
Kim, Irene F.
Soboleva, Alexandra
Tomashevsky, Maxim
Marshall, Kimberly A.
Phillippy, Katherine H.
Sherman, Patti M.
Muertter, Rolf N.
Edgar, Ron
[J]. NUCLEIC ACIDS RESEARCH, 2009, 37 : D885 - D890
[5] Vorinostat enhances the radiosensitivity of a breast cancer brain metastatic cell line grown in vitro and as intracranial xenografts
Baschnagel, Andrew
Russo, Andrea
Burgan, William E.
Carter, Donna
Beam, Katie
Palmieri, Diane
Steeg, Patricia S.
Tofilon, Philip
Camphausen, Kevin
[J]. MOLECULAR CANCER THERAPEUTICS, 2009, 8 (06) : 1589 - 1595
[6] Deletion of histone deacetylase 3 reveals critical roles in S phase progression and DNA damage control
Bhaskara, Srividya
Chyla, Brenda J.
Amann, Joseph M.
Knutson, Sarah K.
Cortez, David
Sun, Zu-Wen
Hiebert, Scott W.
[J]. MOLECULAR CELL, 2008, 30 (01) : 61 - 72
[7] Butler LM, 2000, CANCER RES, V60, P5165
[8] A TRANSCRIPTIONAL CO-REPRESSOR THAT INTERACTS WITH NUCLEAR HORMONE RECEPTORS
CHEN, JD
EVANS, RM
[J]. NATURE, 1995, 377 (6548) : 454 - 457
[9] Clarke AS, 1999, MOL CELL BIOL, V19, P2515
[10] Structural insights into the interaction and activation of histone deacetylase 3 by nuclear receptor corepressors
Codina, A
Love, JD
Li, Y
Lazar, MA
Neuhaus, D
Schwabe, JWR
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2005, 102 (17) : 6009 - 6014

← 1 2 3 4 5 6 7 →