The interplay between BRCA1 and 53BP1 influences death, aging, senescence and cancer.
In proliferating cells DNA double strand breaks (DSBs) are a common occurrence during DNA replication. DSB repair using homologous recombination is essential for the error-free repair of such breaks and proliferating cells require some level of HR activity for their viability. The BRCA1 tumour suppressor has an important role in this process and is believed to channel the DSBs into the HR pathway. The related 53BP1 gene is known to positively regulate repair of DSBs outside of S phase, but via the NHEJ pathway. Two new studies suggest a new role for 53BP1 as an inhibitor of HR [1,2]. These genetic studies establish that 53BP1, but not other components of the NHEJ machinery, can inhibit the early resection step of HR. In cells defective for BRCA1, which is required for efficient HR, the balance between promoting and inhibiting HR is thrown towards inhibition. Simultaneous loss of 53BP1 can rescue the HR defect of BRCA1-defective cells and restore cellular viability. Here, I provide an overview of these studies and discuss their implications for tumourigenesis.
Lowndes
Noel F
NF
Genome Stability Laboratory, Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland Galway, University Road, Glaway, Ireland. noel.lowndes@nuigalway.ie
D000818:Animals; D019313:BRCA1 Protein / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics*; D002453:Cell Cycle; D002470:Cell Survival; D002868:Chromosomal Proteins, Non-Histone; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D011995:Recombination, Genetic; D012689:Sequence Homology, Nucleic Acid; D000071857:Tumor Suppressor p53-Binding Protein 1
D019313:BRCA1 Protein; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C498301:TP53BP1 protein, human; C498302:Trp53bp1 protein, mouse; D000071857:Tumor Suppressor p53-Binding Protein 1