Publications by authors named "Michael A Longo"
Article Synopsis
- The BRCA2 protein plays a crucial role in protecting DNA during replication and repairing breaks, working closely with RAD51.
- Researchers determined the crystal structure of the BRCA2 C-terminal interaction-domain (TR2i) with RAD51, discovering it changes RAD51's shape to better accommodate double-stranded DNA rather than supporting its function in break repair.
- The study found that TR2i functions as an allosteric regulator, influencing the shift between replication fork protection and DNA repair, depending on the cell cycle phase.
Article Synopsis
- - GRB2 is a crucial protein that functions both as an adapter for signaling in cells and a protector of DNA, specifically by preventing degradation at stalled replication sites associated with BRCA2.
- - By inhibiting RAD51's ATPase activity, GRB2 stabilizes RAD51 on these stuck replication forks, which is vital for maintaining DNA integrity.
- - In studies involving ovarian cancer models, reducing GRB2 levels during PARP inhibitor treatment led to decreased tumor size and improved survival rates, highlighting its potential as a therapeutic target and biomarker for choosing treatment strategies.
Article Synopsis
- RAD51C is a gene linked to an increased risk of breast, ovarian, and prostate cancers, but its structural and functional roles are not fully understood, limiting mutation interpretations to its function in homology-directed repair (HDR).
- The study provides a co-crystal structure of RAD51C with XRCC3 and ATP analog, revealing important details about RAD51C’s roles in DNA replication stability and its potential interaction interfaces related to cancer mutations.
- The findings suggest that RAD51C contributes to DNA replication stress response and could help in understanding how certain mutations may lead to tumor development, aiding in the categorization and functional testing of cancer-related mutations.
Proc Natl Acad Sci U S A
October 2013
Article Synopsis
- DNA synthesis during genomic duplication starts with primase, an enzyme that creates RNA primers necessary for initiating DNA replication.
- In eukaryotic cells, primase works closely with DNA polymerase α to extend these RNA primers and manage the discontinuous DNA replication process on the lagging strand.
- The study presents the crystal structure of human primase, revealing its architecture and how it interacts with DNA polymerase α, which is crucial for stabilizing primase at the replication fork.
