Regulatory and Functional Involvement of Long Non-Coding RNAs in DNA Double-Strand Break Repair Mechanisms

Round 1

Reviewer 1 Report

In this manuscript, the authors gave an extensive review of lncRNAs (long non-coding RNAs) involved in DNA damage response (DDR).  Overall the manuscript is well written and carries useful information to readers who may be interested in this topic.

Major critiques:

  None

Minor critiques:

1. DDR on the cellular level is executed roughly through several stages: (a) DSB (double strand break) sensing by sensors, (b) signal transduction by transducer complexes, (c) damage repair by effector molecules, and (d) downstream global responses (e.g. p53-induced transcription). The authors should consider to (a) provide a proper introduction in the context listed above, (b) add a figure like figure 1 to illustrate how lncRNAs affect the stages above (esp. stages a-c which are upstream events), and (c) change the order of section 4 to match the natural occurring events listed above (DDR stages a-d) so the readers can appreciate the importance of lncRNA as DDR is expanding from the DSB site to across all cellular space.
2. The introduction on lncRNA can be abridged with subsection titles removed, so focus can be quickly shifted to the major topics.
3. The conclusion part can be made concise to exclude unnecessary information (move to introduction). In the current form, the readers will not be able to figure out easily where the conclusion is located in this section.
4. Figure 2 should be removed as this did not convey any new information to the readers (they already knew all these).

Author Response

We would like to thank the reviewer for her/his time and effort to provide constructive comments to improve our manuscript.

 

Point 1. DDR on the cellular level is executed roughly through several stages: (a) DSB (double strand break) sensing by sensors, (b) signal transduction by transducer complexes, (c) damage repair by effector molecules, and (d) downstream global responses (e.g. p53-induced transcription). The authors should consider to (a) provide a proper introduction in the context listed above, (b) add a figure like figure 1 to illustrate how lncRNAs affect the stages above (esp. stages a-c which are upstream events), and (c) change the order of section 4 to match the natural occurring events listed above (DDR stages a-d) so the readers can appreciate the importance of lncRNA as DDR is expanding from the DSB site to across all cellular space.

 

Response: We would like to thank the reviewer for the suggested restructuring of the text of our manuscript. As proposed:

• Throughout the manuscript we adopted a structured presentation of the lncRNAs oriented to reflect the stages of the DDR.
• A new Figure 1 was included that depicts the involvement of lncRNAs in DDR based on its deployment stages
• Section 4 was revised following the reviewer’s recommendation

 

Point 2. The introduction on lncRNA can be abridged with subsection titles removed, so focus can be quickly shifted to the major topics.

 

Response: As suggested, the introduction on lncRNAs was reformatted accordingly.

 

Point 3.The conclusion part can be made concise to exclude unnecessary information (move to introduction). In the current form, the readers will not be able to figure out easily where the conclusion is located in this section.

 

Response: We thank the reviewer for this point. Conclusion has been reduced at a more concise level, while previous information has been included in a separate new section.

 

Point 4. Figure 2 should be removed as this did not convey any new information to the readers (they already knew all these).

 

Response: Old Figure 2 has been removed. Previous Figure 1 has been renumbered as new Figure 2, and a new Figure 1 has been included as requested in point 1.

 

We thank once more the reviewer for the constructive comments and suggestions, and hope they are satisfactory.

Reviewer 2 Report

In this review, the author very concisely explained the role of lncRNAs in Double-strand break and repair.

It is a well-written review, with minor spelling and grammatical errors,

The author should provide a more pictorial explanation, the 2 figure provided does not explain any mechanism or pathways.  include more figures to explain each of the mechanisms lncRNA involved.

The author has to include figures to explain the mechanism to show how lncRNA are involved, I believe the Figures speak more than the explanation, this is major flaw in the manuscript, which the author has to provide.

 

Author Response

We would like to thank the reviewer for her/his supportive remarks and time and effort to provide constructive comments to improve our manuscript.

 

As suggested by the reviewer, and also requested by the other reviewer, Figure 2 was deleted. Initial Figure 1 was renumbered as new Figure 2, while a more descriptive Figure 1 was included. Particularly, the new Figure 1 was built to reflect the involvement of the lncRNAs at all stages comprising the DDR network. This modification was also implemented also in section 4 of the manuscript.

 

We thank once more the reviewer for the constructive comments and suggestions, and hope they are satisfactory.

Round 2

Reviewer 2 Report

none

Author Response

We thank the reviewer for his/her positive outcome.