St. Jude researchers discover new role for PARP1 enzyme in DNA repair

Scientists at St. Jude Children's Research Hospital have identified a previously unknown mechanism by which the enzyme poly (ADP-ribose) polymerase (PARP1) facilitates DNA repair. According to research published in Molecular Cell, PARP1 performs a third, undescribed role beyond its known functions of sensing DNA damage and signaling for repair.

The study reveals that PARP1 assists in chromatin remodeling by disassembling nucleosomes to increase chromatin accessibility for downstream repair mechanisms. Researchers found that PARP1 asymmetrically evicts two histone proteins near the site of DNA damage, transforming the standard eight-protein nucleosome into a six-protein structure known as a hexasome. This process partially opens the nucleosome to allow repair to proceed.

Understanding this mechanism may have significant implications for cancer treatment, as inhibiting DNA damage repair can be therapeutically beneficial in certain cancers with specific genetic vulnerabilities.