Publications by authors named "Anthony M Couturier"
Article Synopsis
- The tumor suppressor PALB2 plays a crucial role in repairing DNA damage by enhancing RAD51-mediated homologous recombination and safeguarding active genes from replication stress.
- Acetyltransferases KAT2A/2B modify a specific cluster of lysine residues (the 7K-patch) in PALB2, which influences its binding to chromatin and promotes its connection to nucleosomes in normal conditions.
- However, upon DNA damage, the acetylation is reversed, leading to increased mobility of PALB2; mutations in the 7K-patch disrupt PALB2's chromatin binding, impair RAD51 function, and heighten DNA damage during S phase, which reduces cell survival.
Article Synopsis
- The DNA damage response (DDR) helps cells survive damage and needs certain chemical changes to work properly.
- A specific enzyme called SET7 is important for DDR, and when cells don’t have it, they can get hurt more by cancer treatments.
- Researchers found that SET7 adds a special mark (methylation) to a protein named FEN1, which helps with DNA copying, making it essential for the cell to handle stress during this process.
The partner and localiser of BRCA2 (PALB2) plays important roles in the maintenance of genome integrity and protection against cancer. Although PALB2 is commonly described as a repair factor recruited to sites of DNA breaks, recent studies provide evidence that PALB2 also associates with unperturbed chromatin. Here, we investigated the previously poorly described role of chromatin-associated PALB2 in undamaged cells.
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- Fanconi anemia (FA) is a rare genetic disorder that causes problems like bone marrow failure and a higher chance of getting cancer.
- A key protein in this process is called FANCD2, which helps the cell deal with DNA damage.
- Researchers found important areas on FANCD2 that help it bind to DNA and get into the cell's nucleus, and changes in these areas can make the protein less effective in fighting DNA damage.
DNA double-strand breaks (DSB) elicit a ubiquitylation cascade that controls DNA repair pathway choice. This cascade involves the ubiquitylation of histone H2A by the RNF168 ligase and the subsequent recruitment of RIF1, which suppresses homologous recombination (HR) in G1 cells. The RIF1-dependent suppression is relieved in S/G2 cells, allowing PALB2-driven HR to occur.
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- Researchers studied a gene called PALB2, which helps prevent cancer by stopping tumor growth. Mutations in this gene can make people much more likely to get breast cancer, with risks increasing significantly by age 40.
- The study looked at different mutants of PALB2 and found that one specific mutant (W1038X) could still help in a process important for DNA repair, even though it behaved differently than normal.
- They discovered that this mutant also changed how the PALB2 protein moves in and out of the cell, linking this change to an increase in cancer risk.
APRIN (PDS5 cohesin associated factor B) interacts with both the cohesin complex and the BRCA2 tumor suppressor. How APRIN influences cohesion and DNA repair processes is not well understood. Here, we show that APRIN is recruited to DNA damage sites.
View Article and Find Full Text PDFFor decades, radiotherapy and chemotherapy were the two only approaches exploiting DNA repair processes to fight against cancer. Nowadays, cancer therapeutics can be a major challenge when it comes to seeking personalized targeted medicine that is both effective and selective to the malignancy. Over the last decade, the discovery of new targeted therapies against DNA damage signalling and repair has offered the possibility of therapeutic improvements in oncology.
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