Abstract
The centromere is a unique chromatin domain that links sister chromatids and forms the attachment site for spindle microtubules in mitosis. Centromere inheritance is largely DNA sequence-independent but strongly reliant on a self-propagating chromatin domain featuring nucleosomes containing the H3 variant CENP-A. Unlike other histones, CENP-A is maintained with unusually high stability in chromatin. Previously, we have shown that mitotic maintenance of CENP-A and other constitutive centromere-associated network (CCAN) proteins is controlled by a dynamic SUMO cycle and that the deSUMOylase SENP6 is necessary for stable maintenance of CENP-A at the centromere. Here, we discover that the removal of SENP6 leads to a rapid loss of the CCAN, followed by a delayed loss of centromeric CENP-A, indicating that the CCAN is the primary SUMO target. We found that the ATP-dependent segregase p97/VCP removes centromeric CENP-A in a SUMO-dependent manner and interacts physically with the CCAN and CENP-A chromatin. Our data suggest a direct role of p97 in removing centromeric CENP-A via SUMOylated CCAN proteins, thereby ensuring centromere homeostasis and potentially preventing ectopic CENP-A accumulation.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
