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Date & Time: 13th February 2024 (Tuesday), 5:00 p.m. to 6:00 p.m.
Venue: C V Raman Hall, IISER Tirupati Transit Campus
Title: “How cells protect their DNA from damage: role of epigenetic mechanisms in maintenance of genomic integrity”.
Speaker: Dr. Devyani Haldar,
Staff Scientist-VI,
Head, Laboratory of Chromatin Biology & Epigenetics,
CDFD, Hyderabad, India.
Abstract:
The DNA of all organisms faces damage due extrinsic and intrinsic environmental factors. Packaging of eukaryotic genome into chromatin is a major obstacle to cells encountering DNA damage caused by external or internal agents. For maintaining genomic integrity, the damaged DNA must be efficiently repaired, as if left unrepaired, it leads to genomic instability, a hallmark of cancer and other diseases. Therefore, the DNA damages have to be detected in chromatin context, the DNA damage response (DDR) pathways have to be activated to repair the damaged DNA by various DNA repair pathways such as base excision repair, Nucleotide excision repair, Double strand break repair pathways such as non‐ homologous end joining and homologous recombination repair. How cell detect specific types of damage and how specific DNA repair pathways are activated and directed towards the site of damage are interesting questions that are being researched on currently. Epigenetic mechanisms are emerging as regulator of genomic integrity in addition to their role in gene regulation. It is becoming clearer now that chromatin is not a mere hindrance to DDR, it plays active role in sensing, detection and repair of DNA damage. DNA breaks induce many types of histone modifications, such as phosphorylation, acetylation, methylation and ubiquitylation on specific histone residues which are signal and context dependent. DNA break induced histone modifications have been reported to function in sensing the breaks, activating processing of breaks by specific pathways, and repairing damaged DNA to ensure integrity of the genome. Following DNA damage, favourable environment for DNA repair is created by generating open and relaxed chromatin structure. It has been proposed that histone acetylation may contribute by either opening up the chromatin to make it more accessible to the damage signaling and repair machinery or recruit proteins involved in these processes. At sites of damage, acetylation is a transient effect; histone deacetylation is concomitant with DNA damage repair. The Sir2 family NAD-dependent histone deacetylases function in many cellular processes including DNA damage signaling, replication stress response and repair. However, how the DNA damage signaling and DNA repair proteins coordinate with the chromatin regulators to bring about specific type of repair is not very well understood. We are studying how histone acetylation and deacetylases are tightly regulated by checkpoint kinases such as ATR/rad3 and how these proteins co-ordinate the initial events are involved in recruitment of DSB repair proteins to their site of action at the DSB to facilitate repair. I will discuss recent work on the understanding on the critical role of histone acetylation and sirtuin family deacetylases in DNA replication stress response in inducing changes both in chromatin reorganization and promoting recruitment of DSB repair proteins to sites of DNA damage.
Biosketch:
EDUCATION
2001 Ph.D. Department of Biochemistry, Indian Institute of Science, Bangalore, India
1994 M. Sc. Center for Biotechnology, Jawaharlal Nehru University, New Delhi, India
1992 B.Sc. Chemistry (Hons.) Barkatullah University, Bhopal, M P, India.
2002-2006 Postdoctoral visiting Fellowship at National Institutes of Health (NIH),
Bethesda, USA
PROFESSIONAL AND RESEARCH EXPERIENCE
2013 – till date Staff Scientist-VI and Group Head, Laboratory of Chromatin, Biology &
Epigenetics, CDFD, Uppal, Hyderabad
2006-2013 Principal Research Scientist (Faculty), Department of Biology, Dr.
Reddy’s Institute of Life Sciences, Hyderabad
RESEARCH INTERESTS
Role of epigenetic modifications in regulation of DNA replication, DNA damage response and repair, their contribution to maintenance of genomic integrity and implications in cancer progression. Understanding the molecular functions and regulation of Sirtuin family NAD+-dependent protein deacetylases in DNA metabolism, cell physiology and metabolism.
