www.landesbioscience.com Cell Cycle 1653

Cellular senescence is a state of stable cell growth arrest. Activation of oncogenes in primary mammalian cells typically triggers cellular senescence. Oncogene-induced senescence is an important tumor suppression mechanism, driving stable growth arrest of cancer progeni-tor cells harboring the initial oncogenic hit. Chromatin in the nuclei of senes-cent human cells is often reorganized to form specialized domains of facultative heterochromatin, known as senescence-associated heterochromatin foci (SAHF).1 SAHF contribute to senescence-associated cell growth arrest by sequestering and silencing proliferation-promoting genes such as the E2F target gene cyclin A.1 Notably, SAHF are different from consti-tutive heterochromatin, such as pericen-tromeres, which are largely excluded from SAHF.1 BRCA1 has been implicated in regu-lating chromatin structure. For example, oncogene-induced BRCA1 chromatin dis-sociation is known to regulate SAHF for-mation during senescence.2 Consistently, it has been demonstrated that BRCA1 causes large-scale chromatin de-conden-sation.3 In contrast, BRCA1 is implicated in regulating pericentromeric heterochro-matin by silencing the repetitive satellite transcripts through ubiquitination of his-tone H2A.4 This suggests that BRCA1 may function to antagonize or promote heterochromatin formation in a genomic locus-specific manner. BRCA1 interacts with BRG1 in trans-formed cells. BRG1 is the catalytic subunit of the SWI/SNF chromatin-remodeling complex. BRG1 is known to regulate heterochromatin structure. For example, similar to the effects of BRCA1 loss on pericentromeres, it has been previousl