Poly ADPRibose Polymerase 1231 PARP Structure and Function

Sperm DNA integrity is critical for successful embryo development and the transmission of intact genetic material to the offspring [2]. During spermatogenesis, protection of the sperm DNA is achieved by tight packaging into a condensed chromatin. Incomplete chromatin condensation and persistence of DNA strand breaks during spermatogenesis are associated with DNA damage and male infertility [65], PARP, a DNA damage repair enzyme, has been first introduced by Chambon et al. in 1963. It is associated with chromatin and specifically found in the nucleolus [66]. To date, 18 different PARP homologues have been identified, but the structure and function of some are not known yet [67]. Each PARP family member has a catalytic part which contains 50 amino acids that act as the "PARP signature" [67]. PARP family members have other domains, such as DNA-binding domains (DBDs), ankyrin repeats, WWEs domain, macro domains, and BRCA-1 domain with C terminus which is activated following DNA damage [68]. PARP proteins detect DNA strand breaks and have a particular role in both the base excision repair (BER) and nucleotide repair pathways [69]. They have been shown in testicular germ cells [69, 70],

Members of the PARP family have been categorized according to the functional domain. The first category includes PARP1 and PARP2 is activated in response to DNA strands break. Tankyrases 1 and 2 are in second group and have different functions such as telomere regulation and mitotic segregation. The third group consists of PARP12, PARP13, and TCDD-inducible PARP, which contain CCCH-type zinc fingers. Finally, the fourth group includes PARP9, PARP14, and PARP15 which have 1-3 macro domains connected to a PARP domain. They have WWE domain and a catalytic function. For other PARPs such as PARP8, 11, 16, and PARP6, no domains have been found, except a WWE domain in PARP11, therefore it is difficult to define any possible functional role for them [71].

PARP family members were recently classified on the basis of their catalytic domain sequences by Hassa and Hottiger [72]. They were divided into three groups: group 1 including PARP1, PARPb (short PARP1), PARP2, and PARP3; group 2 consists of PARP4; and group 3 consists of two PARP members, tankyrase-1, tankyrase

ADPR

ADPR ADPR ADPR

ADPR ADPR

DNA binding domain

(1-373 amino acids)

Site of Cleavage

Automodification domain

(374-533 amino acids)

Catalytic domain (534-1014 amino acids)

Full length PARP (113 kDa)

Short fragment (24 kDa)

Long fragment (89 kDa)

Cleaved PARP Fragments

Fig. 12.1 Structural domains of PARP and its fragments. (a) DNA-binding domain containing Zinc fingers (F1-3) for nucleosome binding and nuclear localization (NLS) segment; Automodification domain responsible for adding ADPR (ADP-ribose) polymers through binding with Lysine (K) amino acid and catalytic domain has the PARP signature and PARP enzymatic activity. (b) Full-length PARP1 113 kDa molecule with a mark on the site of cleavage (214/215 amino acids). (c) PARP cleavage by caspase showing short (24 kDa) and long (89 kDa) cleaved PARP fragments [2]

2a, and its isoform tankyrase-2b, known as PARP5 and PARP6a/b [72]. The prototype enzyme of the PARP family is PARP1, a 113 kDa enzyme encoded by the ADP-ribosyl transferase (ADPRT) gene that sited on chromosome 1 in humans [67],

Pregnancy Guide

Pregnancy Guide

A Beginner's Guide to Healthy Pregnancy. If you suspect, or know, that you are pregnant, we ho pe you have already visited your doctor. Presuming that you have confirmed your suspicions and that this is your first child, or that you wish to take better care of yourself d uring pregnancy than you did during your other pregnancies; you have come to the right place.

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