A recent study in Nature uncovers new functions of BRCA1 that may underlie tumorigenesis in BRCA1-deficient individuals.

BRCA1 is a well-known tumor suppressor, and its loss is a common driver of familial breast and ovarian cancer. BRCA1 activities in normal cells lie at the core of the cellular pathways that maintain genomic integrity throughout DNA replication and in response to stress. But how its disparate functions contribute to its tumor suppressor role is just starting to be elucidated.

Zhu et al. (doi:10.1038/nature10371, 8 September) observed that BRCA1 deficiency led to chromatin disorganization at heterochromatic centers where noncoding, potentially harmful DNA repeat sequences, called satellites, are tightly packed away. Heterochromatin silences the expression of satellite repeats, and the authors found that BRCA1's histone-modifying activity is important for the gagging function of the heterochromatic structures. In the absence of BRCA1, the normally silent satellites are expressed and can run amok, causing genomic instability.

The authors also show that deregulated expression of heterochromatic repeats is present in human breast tumors and that expression of satellite repeats in mammary epithelial cells can drive the initial stages of malignant cellular transformation. Thus, this work not only provides a new view of how BRCA1 deficiency can lead to tumor formation but also highlights the contribution of seemingly inert DNA repeats to tumorigenesis.