Trans-Lesion Synthesis (TLS) is a DNA damage tolerance mechanism that involves recruitment of specialized Y-family DNA polymerases to stalled replication-forks. Once recruited to damaged DNA, TLS polymerases perform post-replication repair synthesis, thereby preventing accumulation of single-stranded discontinuities in genomic DNA. TLS is an inherently error-prone process that can lead to mutations. Therefore TLS must be stringently regulated to prevent genetic instability. Rad18 is an E3 Ubiquitin Ligase that facilitates recruitment of TLS polymerases to sites of DNA damage. Additionally, Rad18 promotes DNA repair via other pathways independently of its roles in TLS. Rad18 is heavily phosphorylated by several protein kinases that are known regulators of both cell cycle control and the DNA damage response. Our recent work shows that Rad18 phosphorylation is important for coupling TLS with cell cycle progression and for dictating choice of DNA repair pathway thereby enforcing DNA damage tolerance and genome stability. 

Integrating translesion synthesis (TLS) and DNA damage tolerance with the cell cycle

244th National Meeting (2012)

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