IISER Pune
INDIAN INSTITUTE OF SCIENCE EDUCATION AND RESEARCH (IISER) PUNE
where tomorrow’s science begins today
An Autonomous Institution, Ministry of Human Resource Development, Govt. of India
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Seminars and Colloquia

Biology

Remodeling of DNA replication forks - Implications in tumorigenesis and chemoresistance  
 
Thu, Jan 25, 2018,   11:00 AM to 12:00 PM at Seminar Room 34, 2nd Floor, Main Building

Dr. Arnab Ray Chaudhuri
Erasmus University Medical Center, The Netherlands

The DNA replication process is an essential, but dangerous process that cells have to undergo for continued proliferation. Disruption of the replication process, results in a failure in the maintenance of the integrity of replicating chromosomes resulting genome instability, which is a driving factor for tumorigenesis. Furthermore, most of the common anti-cancer drugs also interfere with the mechanism of DNA replication, relying on the generic observation that cancer cells, intrinsically deficient for DNA repair are sensitized to DNA damaging agents. Proteins involved in the repair of double stranded breaks (DSB) and DNA crosslinks via the homologous recombination (HR) pathway have also evolved to protect cells from proliferation associated DNA damage by stabilization of the DNA replication forks and protecting them from nuclease mediated processing. A major focus for the past years have been on mutations in Breast Cancer (BRCA) genes which predisposes individuals to breast, ovarian and prostate cancers which has primarily been linked to defects in DSB repair through HR. Furthermore, DNA repair defects have also been identified in sporadic cancers. This has resulted in efforts to identify unknown mutations in genes which could lead to DNA repair defects. However, there is very little information available on how these proteins affect replication fork stability and if they could act in concert with other known HR factors in maintenance of genome stability to prevent tumorigenesis. We use the genetic tractability of the mouse model organism with a combination of unique structural, biochemical and cell biological approaches to gain deeper insights into the mechanisms that that underlie the stabilization of the DNA replication machinery, thus resulting in genome stability.

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