Overlapping in short motif sequences for binding to human REV7 and MAD2 proteins.
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.
Hanafusa
Tomo
T
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.
Habu
Toshiyuki
T
Tomida
Junya
J
Ohashi
Eiji
E
Murakumo
Yoshiki
Y
Ohmori
Haruo
H
D051722:ADAM Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D006801:Humans; D059566:M Phase Cell Cycle Checkpoints; D064246:Mad2 Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D050807:ets-Domain Protein Elk-1 / Q000378:metabolism
D004268:DNA-Binding Proteins; C120552:MAD2L2 protein, human; D064246:Mad2 Proteins; D008565:Membrane Proteins; D050807:ets-Domain Protein Elk-1; D004259:DNA-Directed DNA Polymerase; C118285:REV3L protein, human; D051722:ADAM Proteins; C098339:ADAM9 protein, human