Note for: Werner and Bloom helicases are involved in DNA repair in a complementary fashion

Note for: Werner and Bloom helicases are involved in DNA repair in a complementary fashion
(doi: https://doi.org/10.1038/sj.onc.1205143)

Werner syndrome;

1. rare autosomal recessive disorder

2. premature senescence

Bloom syndrome;

1. short stature

2. immunodeficiency

3. rare autosomal recessive

common for these two;

1. chromosomal instability-->tumorigenesis

WRN and BLM-->closely relate to RecQ helicase

WRN and BLM - involve in DNA repair in a complementary fashion.

Both BLM and WRN;

1. contain 7 signature motifs conserved in DNA/RNA helicases

2. BLM shows most similarity to RecQ subfamily of DNA helicases

Recombinant WRN and BLM;

1. unwind duplex DNA in 3-5 direction with 3' overhang tail

2. both interact with RPA to facilitate the unwinding

WRN has the exonuclease activity (N-terminal) which functions as proofreading during the DNA synthesis.

BLM and WRN show very different profiles of sensitivity toward DNA damaging challenges; 4-NQO, CPT, alkylating agent, X-ray, bleomycin, H2O2, MMS, UV-->from the sensitivities result-->the authors suggested that these two genes play roles in DNA repair, directly or indirectly.

WRN and BLM-

1. suppress increased homologous recombination

2. be able to recognize holliday junction and facilitate the branch migration (act as helicase)

3. suppress HR by disrupting the recombinogenic molecules at stalled replication forks

WRN chicken and human helicase domain;

75%

WRN chicken and human N-terminal exonuclease domain;

73%

Average db times;

WT -- 9 hr

WRN -- 10 hr

BLM -- 12 hr

WRN/BLM -- 13 hr

If the double KO showed more severe results comparing to each-->meaning that each KO pw complement to each other, if only some genotoxic drugs effect, then we say partially complement.

Synergistic increase-->reflecting that each gene works complementary.

UV damage can reflect the ability of cells to fix the damage at the stalled replication folks.

BLM(-/-)

1. increased frequencies in both SCE and targeted genome integration

In conclusion;

1. BLM enhances branch migration of Holliday junctions that encounter stalled replication forks.

2. WRN enhances post-translational recombination repair of dsDNA breaks which occur at the replication forks.

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