2-4 The decision between HR and NHEJ is taken based on the recruitment balance of BRCA1 and 53BP1. ![]() 2īRCA1 is a tumor suppressor that plays an essential role in the DDR through both HR and NHEJ by acting as a scaffold protein in different complexes. 1 Both processes rely on the recruitment of different protein complexes that target the DNA repair. DNA double-strand breaks (DSBs) are the most toxic kind of DNA damage and are primarily repaired through 2 major pathways, the error-free homologous recombination (HR) and error-prone non-homologous end joining (NHEJ). The DNA damage response (DDR) is a major feature in maintaining genome integrity and consequently suppressing tumorigenesis. Human cells are constantly exposed to different DNA damaging insults. These data indicate that CDK9 is a player in the DDR and is consistent with its participation in HR pathway by modulating BRCA1 response. Cells lacking CDK9 are characterized by an altered γ−H2AX foci dynamics after DNA damage, a reduced efficiency in HR but not in NHEJ repair, failure to form BRCA1 and RAD51 IRIF and increased sensitivity to genotoxic agents. Here we show that CDK9 interacts with endogenous BRCA1 and BARD1 mediated by their RING finger and BRCT domains, and describe CDK9 ionizing radiation-induced foci (IRIF) formation and its co-localization with BRCA1 in DNA damage sites. ![]() CDK9 is a component of the positive transcription elongation complex and has been implicated in genome integrity maintenance associated with the replication stress response. Previously, our group identified a putative interaction between BRCA1 and BARD1 (BRCA1-associated RING domain 1) and the cyclin-dependent kinase (CDK9). ![]() BRCA1 and 53BP1, 2 proteins containing the BRCT modular domain, play an important role in DNA damage response (DDR) by orchestrating the decision between HR and NHEJ, but the precise mechanisms regarding both pathways are not entirely understood. Double strand break lesions, the most toxic type of DNA damage, are repaired primarily through 2 distinct pathways: homology-directed recombination (HR) and non-homologous end-joining (NHEJ).
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |