PARP1

PARP1 Background

Poly [ADP-ribose] polymerase 1 is a protein in humans that is encoded by PARP1 gene ^[1]. It is also known as NAD+ ADP-ribosyltransferase 1 or poly[ADP-ribose] synthase 1. PARP1 is involved in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosyl)ation of a limited number of acceptor proteins involved in chromatin architecture and in DNA metabolism. This modification follows DNA damages and appears as an obligatory step in a detection/signaling pathway leading to the reparation of DNA strand breaks. PARP1 is one of six enzymes required for the highly error-prone DNA repair pathway microhomology-mediated end joining (MMEJ) ^[2]. PARP1 is one of six enzymes required for the highly error-prone DNA repair pathway microhomology-mediated end joining (MMEJ) ^[3]. When its promoter region ETS site is epigenetically hypomethylated, PARP1 is over-expressed, contributing to progression to endometrial cancer ^[4] BRCA-mutated ovarian cancer ^[5], and BRCA-mutated serous ovarian cancer ^[6]. PARP1 is also over-expressed in a number of other cancers, including neuroblastoma, HPV infected oropharyngeal carcinoma, testicular and other germ cell tumors, Ewing's sarcoma, malignant lymphoma, breast cancer, and colon cancer.

[1] Ha HC, Snyder SH. Poly(ADP-ribose) polymerase-1 in the nervous system [J]. Neurobiology of Disease. 2000, 7 (4): 225–39.
[2] Sharma S, Javadekar SM, et al. Homology and enzymatic requirements of microhomology-dependent alternative end joining [J]. Cell Death & Disease. 2015, 6 (3): e1697.
[3] Muvarak N, Kelley S, et al. c-MYC Generates Repair Errors via Increased Transcription of Alternative-NHEJ Factors, LIG3 and PARP1, in Tyrosine Kinase-Activated Leukemias [J]. Molecular Cancer Research. 2015, 13 (4): 699–712.
[4] Bi FF, Li D, et al. Hypomethylation of ETS transcription factor binding sites and upregulation of PARP1 expression in endometrial cancer [J]. BioMed Research International. 2013: 946268.
[5] Li D, Bi FF, et al. Poly (ADP-ribose) polymerase 1 transcriptional regulation: a novel crosstalk between histone modification H3K9ac and ETS1 motif hypomethylation in BRCA1-mutated ovarian cancer [J]. Oncotarget. 2014, 5 (1): 291–7.
[6] Bi FF, Li D, et al. Promoter hypomethylation, especially around the E26 transformation-specific motif, and increased expression of poly (ADP-ribose) polymerase 1 in BRCA-mutated serous ovarian cancer [J]. BMC Cancer. 2013, 13: 90.