Regulation of DNA replication - roles of PARP1 and p53

Replication of chromosomal DNA is a fundamental process that requires stringent regulation to ensure accurate, efficient DNA synthesis that duplicates the entire genome. In human cells, thousands of replication origins are coordinately activated during S phase of cell cycle and two DNA strands are locally unfolded, forming a structures called replication forks. Regulation of replication fork speed and activation of origins are main means that allow replication of entire chromosomal DNA. Speed of replication fork progression is controlled by multiple mechanisms, including proteins p53 and PARP1. Considering the importance of DNA replication, little is known about molecular mechanism regulating speed of replication fork. The main goal of proposed study is to investigate the regulatory pathways and functions of PARP1 and p53 in DNA replication.