BRCA1/2 Haploinsufficiency: Exploring the Impact of Losing one Allele.

Since their discovery in the late 20 century, significant progress has been made in elucidating the functions of the tumor suppressor proteins BRCA1 and BRCA2. These proteins play vital roles in maintaining genome integrity, including DNA repair, replication fork protection, and chromosome maintenance. It is well-established that germline mutations in BRCA1 and BRCA2 increase the risk of breast and ovarian cancer; however, the precise mechanism underlying tumor formation in this context is not fully understood.

Replication gap suppression depends on the double-strand DNA binding activity of BRCA2.

Replication stress (RS) is a major source of genomic instability and is intrinsic to cancer cells. RS is also the consequence of chemotherapeutic drugs for treating cancer. However, adaptation to RS is also a mechanism of resistance to chemotherapy.

At the crossroads of RNA biology, genome integrity and cancer.

This article is the synthesis of the scientific presentations that took place during two international courses at Institute Curie, one on post-transcriptional gene regulation and the other on genome instability and human disease, that were joined together in their 2021 edition. This joined course brought together the knowledge on RNA metabolism and the maintenance of genome stability.