Open AccessThe ATAD2/ANCCA homolog Yta7 cooperates with Scm3 HJURP to deposit Cse4 CENP-A at the centromere in yeast
Author(s) -
Sara Shahnejat-Bushehri,
Ann E. EhrenhoferMurray
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.1917814117
Subject(s) - centromere , chromosome segregation , kinetochore , nucleosome , chromatin , biology , chromosome , histone , microbiology and biotechnology , saccharomyces cerevisiae , histone h3 , genetics , dna , yeast , gene
The AAA + ATPase and bromodomain factor ATAD2/ANCCA is overexpressed in many types of cancer, but how it contributes to tumorigenesis is not understood. Here, we report that the Saccharomyces cerevisiae homolog Yta7 ATAD2 is a deposition factor for the centromeric histone H3 variant Cse4 CENP-A at the centromere in yeast. Yta7 ATAD2 regulates the levels of centromeric Cse4 CENP-A in that yta7∆ causes reduced Cse4 CENP-A deposition, whereas YTA7 overexpression causes increased Cse4 CENP-A deposition. Yta7 ATAD2 coimmunoprecipitates with Cse4 CENP-A and is associated with the centromere, arguing for a direct role of Yta7 ATAD2 in Cse4 CENP-A deposition. Furthermore, increasing centromeric Cse4 CENP-A levels by YTA7 overexpression requires the activity of Scm3 HJURP , the centromeric nucleosome assembly factor. Importantly, Yta7 ATAD2 interacts in vivo with Scm3 HJURP , indicating that Yta7 ATAD2 is a cochaperone for Scm3 HJURP The absence of Yta7 causes defects in growth and chromosome segregation with mutations in components of the inner kinetochore (CTF19/CCAN, Mif2 CENP-C , Cbf1). Since Yta7 ATAD2 is an AAA + ATPase and potential hexameric unfoldase, our results suggest that it may unfold the Cse4 CENP-A histone and hand it over to Scm3 HJURP for subsequent deposition in the centromeric nucleosome. Furthermore, our findings suggest that ATAD2 overexpression may enhance malignant transformation in humans by misregulating centromeric CENP-A levels, thus leading to defects in kinetochore assembly and chromosome segregation.