(November 13, 2019) A study recently published in Nature Communications and led by OCRA grantee Dr. Rugang Zhang showed that the ARID1A protein plays a fundamental role in ensuring correct chromosome segregation when the cells divide.
Specifically, ARID1A controls expression of another protein called STAG1 that is required to keep chromosome ends together. When ARID1A function is lost due to mutations, the levels of STAG1 decrease and, as a consequence, cells accumulate gross chromosomal alterations that are not compatible with cell survival. Loss of ARID1A therefore pushes a selection process that favors cells lacking genomic instability.
Although ARID1A is known to act as a guardian of genome integrity, researchers could not explain why cancer types with high frequency of ARID1A mutations are not typically associated with genomic instability. “Our findings may elucidate this apparent paradox and partly explain why clear cell ovarian cancers typically respond poorly to chemotherapy agents that target cell division,” said Dr. Zhang.