A requirement for STAG2 in replication fork progression creates a targetable synthetic lethality in cohesin-mutant cancers.

Cohesin is a multiprotein ring that is responsible for cohesion of sister chromatids and formation of DNA loops to regulate gene expression. Genomic analyses have identified that the cohesin subunit STAG2 is frequently inactivated by mutations in cancer. However, the reason STAG2 mutations are selected during tumorigenesis and strategies for therapeutically targeting mutant cancer cells are largely unknown. Here we show that STAG2 is essential for DNA replication fork progression, whereby STAG2 inactivation in non-transformed cells leads to replication fork stalling and collapse with disruption of interaction between the cohesin ring and the replication machinery as well as failure to establish SMC3 acetylation. As a consequence, STAG2 mutation confers synthetic lethality with DNA double-strand break repair genes and increased sensitivity to select cytotoxic chemotherapeutic agents and PARP or ATR inhibitors. These studies identify a critical role for STAG2 in replication fork procession and elucidate a potential therapeutic strategy for cohesin-mutant cancers

Existing practices, alternatives

Improvement can be successful if participants\u27 needs are met

Guide to Nyanza Province microfilm collection, Kenya National Archives, Part III: Section 10, Daily correspondence and reports, 1930-1963, Vol. II

This bibliographical list constitutes Volume II of Section 10 of the Nyanza Province daily correspondence and reports, 1930-1963, of the Kenya National Archives. For more information, refer to the Kenya National Archives subject guide.https://surface.syr.edu/archiveguidekenya/1005/thumbnail.jp

Guide to Nyanza Province Microfilm Collection, Kenya National Archives, Part III: Section 10, Daily Correspondence and Reports, 1930-1963, Vol. II

This bibliographical list constitutes Volume II of Section 10 of the Nyanza Province daily correspondence and reports, 1930-1963, of the Kenya National Archives

Guide to Nyanza Province microfilm collection, Kenya National Archives, Part III: Section 10, Daily correspondence and reports, 1930-1963, Vol. I

This guide to the Nyanza Province microfilm collection of the Kenya National Archives consists of daily correspondence and reports for the Province from 1930 to 1963. It pertains to Section 10, the third and most substantial section of the Nyanza Province Archives, and is to be published in two volumes. Like Section 10B, also a predominantly post-1930 collection of documents, the records are arranged and filed according to the departments within the provincial administration to which they pertain. For more information, refer to the Kenya National Archives subject guide.https://surface.syr.edu/archiveguidekenya/1004/thumbnail.jp

Guide to Nyanza Province Microfilm Collection, Kenya National Archives, Part III: Section 10, Daily Correspondence and Reports, 1930-1963, Vol. I

This guide to the Nyanza Province microfilm collection of the Kenya National Archives consists of daily correspondence and reports for the Province from 1930 to 1963. It pertains to Section 10, the third and most substantial section of the Nyanza Province Archives, and is to be published in two volumes. Like Section 10B, also a predominantly post-1930 collection of documents, the records are arranged and filed according to the departments within the provincial administration to which they pertain

Guide to Nyanza Province microfilm collection, Kenya National Archives, Part I: Section 10B, Correspondence and reports 1925-1960

The Nyanza Province microfilm collection of the Kenya National Archives consists of microfilmed reports and correspondence produced by the British colonial administration in the Nyanza Province from 1925 to 1960. These documents, filmed by the Archives\u27 technical staff, are arranged, numbered and filmed according to the functional responsibilities of the colonial administration. For more information, refer to the Kenya National Archives subject guide.https://surface.syr.edu/archiveguidekenya/1002/thumbnail.jp

Guide to Nyanza Province Microfilm Collection, Kenya National Archives, Part I: Section 10B, Correspondence and Reports 1925-1960

The Nyanza Province microfilm collection of the Kenya National Archives consists of microfilmed reports and correspondence produced by the British colonial administration in the Nyanza Province from 1925 to 1960. These documents, filmed by the Archives\u27 technical staff, are arranged, numbered and filmed according to the functional responsibilities of the colonial administration

Guide to Nyanza Province microfilm collection, Kenya National Archives, Part III: Section 10, Daily correspondence and reports, 1930-1963, Vol. I

This guide to the Nyanza Province microfilm collection of the Kenya National Archives consists of daily correspondence and reports for the Province from 1930 to 1963. It pertains to Section 10, the third and most substantial section of the Nyanza Province Archives, and is to be published in two volumes. Like Section 10B, also a predominantly post-1930 collection of documents, the records are arranged and filed according to the departments within the provincial administration to which they pertain. For more information, refer to the Kenya National Archives subject guide.https://surface.syr.edu/archiveguidekenya/1004/thumbnail.jp