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DDR_regulation_by_hMOB2._Cellular_Signalling_2014.pdf (3.5 MB)

Regulation of DNA damage responses and cell cycle progression by hMOB2.

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posted on 2023-06-08, 19:14 authored by Valenti Gomez, Ramazan Gundogdu, Marta Gomez, Lily Hoa, Neelam Panchal, Mark O'DriscollMark O'Driscoll, Alexander Hergovich
Mps one binder proteins (MOBs) are conserved regulators of essential signalling pathways. Biochemically, human MOB2 (hMOB2) can inhibit NDR kinases by competing with hMOB1 for binding to NDRs. However, biological roles of hMOB2 have remained enigmatic. Here, we describe novel functions of hMOB2 in the DNA damage response (DDR) and cell cycle regulation. hMOB2 promotes DDR signalling, cell survival and cell cycle arrest after exogenously induced DNA damage. Under normal growth conditions in the absence of exogenously induced DNA damage hMOB2 plays a role in preventing the accumulation of endogenous DNA damage and a subsequent p53/p21-dependent G1/S cell cycle arrest. Unexpectedly, these molecular and cellular phenotypes are not observed upon NDR manipulations, indicating that hMOB2 performs these functions independent of NDR signalling. Thus, to gain mechanistic insight, we screened for novel binding partners of hMOB2, revealing that hMOB2 interacts with RAD50, facilitating the recruitment of the MRE11-RAD50-NBS1 (MRN) DNA damage sensor complex and activated ATM to DNA damaged chromatin. Taken together, we conclude that hMOB2 supports the DDR and cell cycle progression.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Cellular Signalling

ISSN

0898-6568

Publisher

Elsevier

Issue

2

Volume

27

Page range

326-339

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2014-12-09

First Open Access (FOA) Date

2014-12-09

First Compliant Deposit (FCD) Date

2014-12-08

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