Pre-mRNA processing factors meet the DNA damage response.

摘要: It is well known that DNA damaging agents induce genome instability, but only recently have we begun to appreciate chromosomes are fragile per se and frequently subject breakage. replication further magnifies such fragility, because it leads accumulation of single-stranded DNA. Recent findings suggest chromosome fragility similarly increased during transcription. Transcripts produced by RNA polymerase II (RNAPII) multiple processing steps, including maturation 5’ 3’ ends splicing, followed transport the cytoplasm. starts on nascent transcripts mediated a number diverse proteins ribonucleoprotein particles some which recruited cotranscriptionally through interactions with C-terminal domain RNAPII. This coupling thought maximize efficiency pre-mRNA directly impacts choice alternative splice sites. Mounting evidence suggests lack coordination among different perturbing interaction template, has deleterious effects stability. Thus, in absence proper surveillance mechanisms, transcription could be major source damage cancer. high-throughput screenings human cells budding yeast identified several factors implicated metabolism targets checkpoint kinases: ATM (ataxia telangiectasia mutated) ATR (ATM-Rad3 related) (Tel1 Mec1 yeast, respectively). Moreover, inactivation various induces γH2AX foci, an early sign damage. complex network emerging links repair metabolism. In this review provide comprehensive overview role played cell response maintenance