Helicase enzymes are also critical for making a blueprint of a gene for protein production, a process called transcription.

[14] The amino terminus of WRN is involved in both helicase and nuclease activities, while the carboxyl-terminus interacts with p53, an important tumor suppressor.

[15] Phosphorylation of WRN at serine/threonine inhibits helicase and exonuclease activities which are important to post-replication DNA repair.

[12] Upon its inhibition by a small molecule in cancer cells harboring a high number of microsatellites (MSI-H), WRN becomes SUMOylated, which leads to is ubiquitylation and subsequent degradation.

Without normal Werner protein in the nucleus, cells cannot perform the tasks of DNA replication, repair, and transcription.

Recently, WRN has been identified as a synthetic lethality target in cancers containing a high number of microsatellites.

[20] These microsatellite-high (MSI-H) cancers have defects in their mismatch repair machinery (dMMR), which leads to the expansion of (TA)n dinucleotide repeats in the genome.

These expanded (TA) dinucleotide microsatellites lead to the formation of secondary DNA structures (e.g. G-quadruplex) and rely on WRN to repair these bulky lesions.

[citation needed] The table shows results of analysis of 630 human primary tumors for WRN CpG island hypermethylation.

Cells defective in the WRN gene have a 23-fold reduction in spontaneous mitotic recombination, with especial deficiency in conversion-type events.

[29] These findings suggested that the WRN protein takes part in homologous recombinational repair and in the processing of stalled replication forks.

As shown by Shamanna et al.,[8] WRN is recruited to double-strand breaks (DSBs) and participates in NHEJ with its enzymatic and non-enzymatic functions.

At DSBs, in association with Ku (protein), it promotes standard or canonical NHEJ (c-NHEJ), repairing double-strand breaks in DNA with its enzymatic functions and with a fair degree of accuracy.

WRN inhibits an alternative form of NHEJ, called alt-NHEJ or microhomology-mediated end joining (MMEJ).

[31] NEIL1 recognizes (targets) and removes certain ROS-damaged bases and then incises the abasic site via β,δ elimination, leaving 3′ and 5′ phosphate ends.

If WRN is defective, replication arrest results in accumulation of DSBs and enhanced chromosome fragmentation.

(In the absence of DNA damage or replication fork stalling, WRN protein remains localized to the nucleoli.

[35] This finding suggests that WRN helicase participates in the activation of p53 in response to certain types of DNA damage.