Abstract:
:RECQL5 is one of the five human RecQ helicases, involved in the maintenance of genomic integrity. While much insight has been gained into the function of the Werner (WRN) and Bloom syndrome proteins (BLM), little is known about RECQL5. We have analyzed the recruitment and retention dynamics of RECQL5 at laser-induced DNA double strand breaks (DSBs) relative to other human RecQ helicases. RECQL5-depleted cells accumulate persistent 53BP1 foci followed by γ-irradiation, indicating a potential role of RECQL5 in the processing of DSBs. Real time imaging of live cells using confocal laser microscopy shows that RECQL5 is recruited early to laser-induced DSBs and remains for a shorter duration than BLM and WRN, but persist longer than RECQL4. These studies illustrate the differential involvement of RecQ helicases in the DSB repair process. Mapping of domains within RECQL5 that are necessary for recruitment to DSBs revealed that both the helicase and KIX domains are required for DNA damage recognition and stable association of RECQL5 to the DSB sites. Previous studies have shown that MRE11 is essential for the recruitment of RECQL5 to the DSB sites. Here we show that the recruitment of RECQL5 does not depend on the exonuclease activity of MRE11 or on active transcription by RNA polymerase II, one of the prominent interacting partners of RECQL5. Also, the recruitment of RECQL5 to laser-induced damage sites is independent of the presence of other DNA damage signaling and repair proteins BLM, WRN and ATM.
journal_name
DNA Repair (Amst)journal_title
DNA repairauthors
Popuri V,Ramamoorthy M,Tadokoro T,Singh DK,Karmakar P,Croteau DL,Bohr VAdoi
10.1016/j.dnarep.2012.05.001subject
Has Abstractpub_date
2012-07-01 00:00:00pages
624-35issue
7eissn
1568-7864issn
1568-7856pii
S1568-7864(12)00098-5journal_volume
11pub_type
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