Mediator of DNA damage checkpoint protein 1

Definition:

Required for checkpoint mediated cell cycle arrest in response to DNA damage within both the S phase and G2/M phases of the cell cycle. May serve as a scaffold for the recruitment of DNA repair and signal transduction proteins to discrete foci of DNA damage marked by 'Ser-139' phosphorylation of histone H2AX. Also required for downstream events subsequent to the recruitment of these proteins. These include phosphorylation and activation of the ATM, CHEK1 and CHEK2 kinases, and stabilization of TP53 and apoptosis. ATM and CHEK2 may also be activated independently by a parallel pathway mediated by TP53BP1.

References:

[1]. Grant S Stewart, et al. MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature. 2003 Feb 27;421(6926):961-6. [Content Brief]

[2]. Michal Goldberg, et al. MDC1 is required for the intra-S-phase DNA damage checkpoint. Nature. 2003 Feb 27;421(6926):952-6. [Content Brief]

[3]. Zhenkun Lou, et al. MDC1 regulates DNA-PK autophosphorylation in response to DNA damage. J Biol Chem. 2004 Nov 5;279(45):46359-62. [Content Brief]

[4]. Zhenkun Lou, et al. MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways. Nature. 2003 Feb 27;421(6926):957-61. [Content Brief]

[5]. Xingzhi Xu, et al. NFBD1/KIAA0170 is a chromatin-associated protein involved in DNA damage signaling pathways. J Biol Chem. 2003 Mar 7;278(10):8795-803. [Content Brief]

[6]. Claudia Lukas, et al. Mdc1 couples DNA double-strand break recognition by Nbs1 with its H2AX-dependent chromatin retention. EMBO J. 2004 Jul 7;23(13):2674-83. [Content Brief]

[7]. Aimin Peng, et al. NFBD1, like 53BP1, is an early and redundant transducer mediating Chk2 phosphorylation in response to DNA damage. J Biol Chem. 2003 Mar 14;278(11):8873-6. [Content Brief]

[8]. Zhenkun Lou, et al. Mediator of DNA damage checkpoint protein 1 regulates BRCA1 localization and phosphorylation in DNA damage checkpoint control. J Biol Chem. 2003 Apr 18;278(16):13599-602. [Content Brief]

[9]. Tamara A Mochan, et al. 53BP1 and NFBD1/MDC1-Nbs1 function in parallel interacting pathways activating ataxia-telangiectasia mutated (ATM) in response to DNA damage. Cancer Res. 2003 Dec 15;63(24):8586-91. [Content Brief]

[10]. Yong Lei Shang, et al. NFBD1, a novel nuclear protein with signature motifs of FHA and BRCT, and an internal 41-amino acid repeat sequence, is an early participant in DNA damage response. J Biol Chem. 2003 Feb 21;278(8):6323-9. [Content Brief]

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