TRF 2 | TTAGGG repeat binding factor 2

Telomeric repeat-binding factor 2 also known as TRF2 is a 500 amino acid containing telomere specific protein. This nuclear protein with a HTH myb-type DNA-binding domain is a component of the telomere nucleoprotein complex. Usually present at telomeres in metaphase of the cell cycle, TRF2 is a second negative regulator of telomere length where it protects against end-to-end fusion of chromosomes by binding to the telomeric double-stranded TTAGGG repeat. Absence of TRF2 leads to damage of telomeres which are now no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Thus it plays a role in successful progression through the cell division cycle. TRF2 shows ubiquitous expression in most of the tissues with high expression in spleen, thymus, prostate, uterus, testis, small intestine, colon and peripheral blood leukocytes. A component of the shelterin complex (telosome), TRF2 differs from TERF1 in that its N terminus is basic rather than acidic.

TRF 1 | TTAGGG repeat binding factor 1

TRF1 well known as TTAGGG repeat-binding factor 1 or Telomeric repeat-binding factor 1 is a nuclear protein known to bind the telomeric double-stranded TTAGGG repeat and negatively regulate telomere length and protection. This DNA associated regulatory protein contains a HTH myb-type DNA-binding domain and is known to associate with the mitotic spindle and regulate it. A component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1, TERF1 associates with arrays of double-stranded TTAGGG repeats added by telomerase and protects chromosome ends. It has two isoforms of TRF1 and Pin2 of which Pin2 expression is tightly regulated during the cell cycle. TRF1 colocalizes with telomeric DNA in interphase and metaphase cells and is located at chromosome ends during metaphase.

PARP

Poly (ADP-ribose) polymerase or PARP is an enzyme taking active part in several cellular processes which includes mainly DNA repair and programmed cell death. The PARP family of proteins comprises of seventeen members with different structure and function within in the cell. PARPs are known to polymerize ADP-ribose (PAR) from nicotinamide adenine dinucleotide (NAD) that can be degraded by the enzyme PARG (poly (ADP-ribose) glycohydrolase). Moreover PARPs are also involved in base excision repair and thus repair single-stranded DNA nicks. PARPs are also involved in ATP depletion thus leading to lysis and cell death. PARP mediated post-translational modification of proteins such as CTCF affects the amount of DNA methylation at CpG dinucleotides.

PARP 2

Poly [ADP-ribose] polymerase 2 commonly known as PARP2 is a 583 amino acid containing enzyme belonging to the PARP family with a PARP alpha-helical domain and a PARP catalytic domain that catalyzes a poly (ADP-ribosylation) reaction. A component of base excision repair (BER) complex, PARP2, forms homodimer and heterodimer with PARP1. This nuclear protein functions in the base excision repair (BER) pathway, by catalyzing the poly(ADP-ribosylation) 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 detection/signaling pathway thus repairing DNA strand breaks. The basic residues within the N-terminal region of this protein may bear potential DNA-binding properties, and may be involved in the nuclear and/or nucleolar targeting of the protein. It is widely expressed in actively dividing tissues. Two alternatively spliced transcript variants encoding distinct isoforms have been found.

MBD 3 | Methyl-CpG-binding Domain 3

Methyl-CpG-binding domain protein 3 also known as MBD3 is a nuclear protein belonging to the NURD complex family with a MBD (methyl-CpG-binding) domain. This DNA associated, transcription factor is involved in chromatin remodeling and methylates DNA. MBD3 acts as a transcriptional repressor and plays a role in gene silencing.