DNA repair ADP-ribosylation

dna repair facilitated parp1 recruitment of repair enzymes. repair of single strand break in dna initiated binding of parp1. parp1 binds single-strand breaks , pulls base excision repair intermediates close, leading synthesis of poly-adp ribose. xrcc1 x-ray repair cross complementing protein 1. xrcc1 complexes polynucleotide kinase (pnk) processes dna termini. pcna proliferating cell nuclear antigen serves dna clamp aids in dna polymerase activity (dna pol) fen1 (flap endonuclease 1) recruited remove overhanging 5 flap. last step of dna repair involves dna ligase brings final dna strands in phosphodiester bond.

there many mechanisms repair of damaged double stranded dna. parp1 may function synapsis factor in alternative non-homologous end joining. additionally, has been proposed parp1 required slow replication forks following dna damage , promotes homologous recombination @ replication forks may dysfunctional. possible parp1 , parp3 work in repair of double-stranded dna , has been shown parp3 critical double-stranded break resolution. there 2 hypotheses parp1 , parp3 coincide. first hypothesis states 2 adp-ribosyltransferases serve function each other s inactivity. if parp3 lost, results in single-strand breaks, , recruitment of parp1. second hypothesis suggests 2 enzyme work together; parp3 catalyzes mono-adp ribosylation , short poly-adp ribosylation , serves activate parp1.

the parps have many protein targets @ site of dna damage. ku protein , dna-pkcs both double-stranded break repair components unknown sites of adp-ribosylation. histones protein target of parps. core histones , linker histone h1 adp-ribosylated following dna damage. function of these modifications still unknown, has been proposed adp-ribosylation modulates higher-order chromatin structure in efforts facilitate more accessible sites repair factors migrate dna damage.