Hanafusa Tomo, Habu Toshiyuki, Tomida Junya, Ohashi Eiji, Murakumo Yoshiki, Ohmori Haruo
Institute for Virus Research, Kyoto University, Kyoto 606-8507, JapanRadiation Biology Center, Kyoto University, Kyoto 606-8501, JapanDepartment of Pathology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Genes Cells. 2010 Mar;15(3):281-96. doi: 10.1111/j.1365-2443.2009.01380.x. Epub 2010 Jan 19.
Polζ, a DNA polymerase specialized for translesion DNA synthesis (TLS), is comprised of two subunits, the REV3 catalytic subunit and the REV7 accessory subunit. The human REV7 (hREV7) protein is known to interact with hREV3, hREV1 (another TLS protein) and some other proteins such as ADAM9 (a disintegrin and metalloprotease) and ELK-1 (an Ets-like transcription factor). hREV7 is alternatively termed hMAD2L2, because its primary sequence shows 26% identity to that of hMAD2 that plays crucial roles in spindle assembly checkpoint (SAC) via interactions with hMAD1 or hCDC20. Here, we have investigated the molecular basis for the interactions of hREV7/MAD2L2 and hMAD2 with their binding partners. Our results showed that a short sequence of hREV3 is necessary and sufficient for interaction with hREV7. Surprisingly, hMAD2 also binds to the hREV7-binding sequence in hREV3, whereas hMAD2 does not bind to a similar sequence in ADAM9 or ELK-1 and hREV7 does not bind to the hMAD2-binding sequence in hMAD1 or hCDC20. We discuss how hREV7 and hMAD2 recognize their binding partners, and how hREV3 and hREV7 might be involved in SAC.
聚合酶ζ是一种专门用于跨损伤DNA合成（TLS）的DNA聚合酶，由两个亚基组成，即REV3催化亚基和REV7辅助亚基。已知人类REV7（hREV7）蛋白可与hREV3、hREV1（另一种TLS蛋白）以及其他一些蛋白相互作用，如ADAM9（一种解整合素和金属蛋白酶）和ELK-1（一种Ets样转录因子）。hREV7也被称为hMAD2L2，因为其一级序列与hMAD2有26%的同源性，hMAD2通过与hMAD1或hCDC20相互作用在纺锤体组装检查点（SAC）中发挥关键作用。在此，我们研究了hREV7/MAD2L2和hMAD2与其结合伴侣相互作用的分子基础。我们的结果表明，hREV3的一段短序列对于与hREV7相互作用是必要且充分的。令人惊讶的是，hMAD2也与hREV3中的hREV7结合序列结合，而hMAD2不与ADAM9或ELK-1中的类似序列结合，hREV7也不与hMAD1或hCDC20中的hMAD2结合序列结合。我们讨论了hREV7和hMAD2如何识别它们的结合伴侣，以及hREV3和hREV7可能如何参与SAC。
