![]() ![]() In addition, ARID1A interacts with topoisomerase IIa (TOP2A) that resolves sister chromatids linked by catenated DNA strands during mitosis 7. The ARID1A containing BAF complex remodels chromatin structure in an ATP dependent manner to modulate a number of processes that require DNA access such as transcription, DNA damage repair and replication 6. Over 90% of ARID1A mutations in OCCCs are either frame-shift or nonsense, which leads to loss of ARID1A protein expression 3, 4, 5. ARID1A functions as a tumor suppressor in OCCCs. For example, ARID1A is mutated in up to 60% of ovarian clear cell carcinomas (OCCCs) 3, 4, 5. Together, these results show that ARID1A inactivation is selective against gross chromosome aberrations through causing defects in telomere cohesion, which reconciles the long-standing paradox between the role of ARID1A in maintaining mitotic integrity and the lack of genomic instability in ARID1A-mutated cancers.Ī RID1A, encoding a subunit of the BAF (mammalian SWI/SNF) complex, is among the genes that are most frequently mutated in human cancers 1, 2. ![]() Compared with ARID1A wild-type tumors, ARID1A-mutated tumors display significantly less CNAs across multiple cancer types. This correlates with an increase in apoptosis and a reduction in tumor growth. Colony formation capability of single cells in G 2/M, but not G 1 phase, is significantly reduced by ARID1A inactivation. ARID1A inactivation causes telomere damage that can be rescued by STAG1 expression. ARID1A promotes the expression of cohesin subunit STAG1 that is specifically required for telomere cohesion. Here, we show that ARID1A inactivation causes defects in telomere cohesion, which selectively eliminates gross chromosome aberrations during mitosis. ![]() Paradoxically, cancers with high ARID1A mutation rates typically lack copy number alterations (CNAs). ARID1A inactivation causes mitotic defects. ![]()
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