alexa Mechanism Of Action Of Hdac1,2 Selective Inhibitors On DNA Replication? Therapeutic Implications In Cancer Therapy
ISSN: 2157-7633

Journal of Stem Cell Research & Therapy
Open Access

Like us on:
OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations

700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Share This Page

Additional Info

Loading
Loading Please wait..
 

3rd International Conference and Exhibition on Cell & Gene Therapy
October 27-29, 2014 Embassy Suites Las Vegas, USA

Srividya Bhaskara
Accepted Abstracts: J Stem Cell Res Ther
DOI: 10.4172/2157-7633.S1.009
Abstract
Histone deacetylases 1 and 2 (Hdacs1,2) localize to sites of DNA replication. However, functions for Hdacs1,2 in replication are not known. We used genetic knockdown systems and novel Hdacs1,2-selective inhibitors to systematically determine the contributions of Hdacs1,2 to DNA replication. Knockdown of Hdacs1,2 or inhibition of their activities led to a reduction in the replication fork velocity. Further confirming a role for these enzymes in DNA replication, an increase in replication stress response upon hydroxyurea treatment culminating in DNA damage was observed in cells lacking Hdacs1,2 functions. These observed effects are due to a direct role for Hdacs1,2 in DNA replication as transcription of genes involved in replication or repair are not affected in the absence of Hdacs1,2 activities. We found abrogation of Hdacs1,2 functions affects nascent chromatin structure, as evidenced by the altered sensitivity of newly synthesized DNA to nuclease digestion, and causes an increase in histone acetylation (ac) on chromatin. Specifically, H4K16ac (involved in chromatin compaction) is increased on nascent chromatin in the absence of Hdacs1,2 activities. H4K16ac inhibits the ATPase activity of SMARCA5, an ISWI family chromatin remodeler. We find SMARCA5 associates with nascent DNA and loss of SMARCA5 leads to a decrease in the replication fork velocity similar to the loss or inhibition of Hdacs1,2. Collectively, our studies have revealed important functions for Hdacs1,2 in histone deacetylation, nascent chromatin structure maintenance and regulation of SMARCA5 chromatin remodeler activity, which together are required for the proper progression of the replication fork.
Biography
Bhaskara?s research goal is to understand the functions for histone deacetylases (HDACs) in genome maintenance, with the ultimate objective of using the knowledge to improve the therapeutic benefits of HDAC inhibition as a treatment for cancer. In Dr. Bhaskara?s post-doctoral research, she made the discovery that HDAC inhibitors induce cancer cell death by directly targeting genome stability independent of their effect of on transcription. She showed HDAC inhibitors trigger genotoxic stress and death only in cycling cells, and thereby, provided a mechanistic explanation for how HDAC inhibitors selectively kill rapidly cycling cancer cells and not the quiescent normal cells. Using genetic deletion systems, she further showed novel functions for Hdac3 in DNA repair, DNA replication and chromatin structure maintenance. Collectively, these findings provided a new paradigm for the mode-of-action of HDAC inhibitors, which are FDA-approved drugs for the treatment of cutaneous T-cell lymphomas. As an independent investigator, Dr. Bhaskara?s lab goal is to investigate cellular functions of Hdacs in maintaining genome stability. Dr. Bhaskara did her PhD in Dr. Ranjan Ganguly?s lab in University of Tennessee, Knoxville and performed her post-doctoral training at Vanderbilt University, Nashville in Dr. Scott Hiebert?s lab.
image PDF   |   image HTML
 

Relevant Topics

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2017-18
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri, Food, Aqua and Veterinary Science Journals

Dr. Krish

[email protected]

1-702-714-7001 Extn: 9040

Clinical and Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemical Engineering and Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001 Extn: 9040

Earth & Environmental Sciences

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

General Science and Health care Journals

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics and Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001 Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Informatics Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Material Sciences Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Mathematics and Physics Journals

Jim Willison

[email protected]

1-702-714-7001 Extn: 9042

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001 Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

John Behannon

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001 Extn: 9042

 
© 2008-2017 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
adwords