Mediator of DNA Damage Checkpoint 1 (MDC1) Regulates Mitotic Progression

• DOI: 10.1074/jbc.m109.009191
• Publication Date: 2009-10-14T04:19:45Z
• Authors: Kelly Townsend; Helen Mason; Andrew N. Blackford; Edward S. Miller; J.Ross Chapman; Garry G. Sedgwick; Giancarlo Barone; Andrew S. Turnell; Grant S. Stewart
• Keywords: CDC20; Anaphase-promoting complex; Mitotic exit; Mediator; Spindle checkpoint

Human mediator of DNA damage checkpoint 1 (hMDC1) is an essential component the cellular response to double strand breaks. Recently, hMDC1 has been shown associate with a subunit anaphase-promoting complex/cyclosome (APC/C) (Coster, G., Hayouka, Z., Argaman, L., Strauss, C., Friedler, A., Brandeis, M., and Goldberg, M. (2007) J. Biol. Chem. 282, 32053-32064), key regulator mitosis, suggesting possible role for in controlling normal cell cycle progression. Here, we extend this work show that regulates metaphase-to-anaphase transition through its ability bind directly APC/C modulate E3 ubiquitin ligase activity. In support mitotic progression, depletion by small interfering RNA results metaphase arrest appears be independent both BubR1-dependent signaling pathways ATM/ATR activation. Mitotic cells lacking exhibit markedly reduced levels activity characterized Cdc20, failure Cdc20 CREB-binding protein. We suggest therefore functionally modulating Cdc20-dependent activation APC/C.